Author: "Jakob Zimmermann" - Searchworks@Jio Institute Digital Library Search Results

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41 results on '"Jakob Zimmermann"'

1. Salmonella T3SS-2 virulence enhances gut-luminal colonization by enabling chemotaxis-dependent exploitation of intestinal inflammation

Author: Ersin Gül, Jemina Huuskonen, Andrew Abi Younes, Luca Maurer, Ursina Enz, Jakob Zimmermann, Mikael E. Sellin, Erik Bakkeren, and Wolf-Dietrich Hardt
Subjects: CP: Microbiology, CP: Immunology, Biology (General), QH301-705.5
Abstract: Summary: Salmonella Typhimurium (S.Tm) utilizes the chemotaxis receptor Tsr to exploit gut inflammation. However, the characteristics of this exploitation and the mechanism(s) employed by the pathogen to circumvent antimicrobial effects of inflammation are poorly defined. Here, using different naturally occurring S.Tm strains (SL1344 and 14028) and competitive infection experiments, we demonstrate that type-three secretion system (T3SS)-2 virulence is indispensable for the beneficial effects of Tsr-directed chemotaxis. The removal of the 14028-specific prophage Gifsy3, encoding virulence effectors, results in the loss of the Tsr-mediated fitness advantage in that strain. Surprisingly, without T3SS-2 effector secretion, chemotaxis toward the gut epithelium using Tsr becomes disadvantageous for either strain. Our findings reveal that luminal neutrophils recruited as a result of NLRC4 inflammasome activation locally counteract S.Tm cells exploiting the byproducts of the host immune response. This work highlights a mechanism by which S.Tm exploitation of gut inflammation for colonization relies on the coordinated effects of chemotaxis and T3SS activities.
Published: 2024
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2. Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow

Author: René Riedel, Richard Addo, Marta Ferreira-Gomes, Gitta Anne Heinz, Frederik Heinrich, Jannis Kummer, Victor Greiff, Daniel Schulz, Cora Klaeden, Rebecca Cornelis, Ulrike Menzel, Stefan Kröger, Ulrik Stervbo, Ralf Köhler, Claudia Haftmann, Silvia Kühnel, Katrin Lehmann, Patrick Maschmeyer, Mairi McGrath, Sandra Naundorf, Stefanie Hahne, Özen Sercan-Alp, Francesco Siracusa, Jonathan Stefanowski, Melanie Weber, Kerstin Westendorf, Jakob Zimmermann, Anja E. Hauser, Sai T. Reddy, Pawel Durek, Hyun-Dong Chang, Mir-Farzin Mashreghi, and Andreas Radbruch
Subjects: Science
Abstract: Memory B cells are important for protecting the host from pathogen rechallenge, but their properties and locations remain ill-defined. Here the authors show, using single-cell transcriptomics and repertoire analyses, that mouse spleen and bone marrow host distinct populations of isotype-switched memory B cells to potentially optimize for rapid recall responses.
Published: 2020
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3. Regular testing of asymptomatic healthcare workers identifies cost-efficient SARS-CoV-2 preventive measures

Author: Daniel Sanchez-Taltavull, Violeta Castelo-Szekely, Shaira Murugan, Jonathan I. D. Hamley, Tim Rollenske, Stephanie C. Ganal-Vonarburg, Isabel Büchi, Adrian Keogh, Hai Li, Lilian Salm, Daniel Spari, Bahtiyar Yilmaz, Jakob Zimmermann, Michael Gerfin, Edgar Roldan, Guido Beldi, and UVCM-COVID researchers
Subjects: Medicine, Science
Abstract: Protecting healthcare professionals is crucial in maintaining a functioning healthcare system. The risk of infection and optimal preventive strategies for healthcare workers during the COVID-19 pandemic remain poorly understood. Here we report the results of a cohort study that included pre- and asymptomatic healthcare workers. A weekly testing regime has been performed in this cohort since the beginning of the COVID-19 pandemic to identify infected healthcare workers. Based on these observations we have developed a mathematical model of SARS-CoV-2 transmission that integrates the sources of infection from inside and outside the hospital. The data were used to study how regular testing and a desynchronisation protocol are effective in preventing transmission of COVID-19 infection at work, and compared both strategies in terms of workforce availability and cost-effectiveness. We showed that case incidence among healthcare workers is higher than would be explained solely by community infection. Furthermore, while testing and desynchronisation protocols are both effective in preventing nosocomial transmission, regular testing maintains work productivity with implementation costs.
Published: 2021

4. Resident macrophages acquire innate immune memory in staphylococcal skin infection

Author: Reinhild Feuerstein, Aaron James Forde, Florens Lohrmann, Julia Kolter, Neftali Jose Ramirez, Jakob Zimmermann, Mercedes Gomez de Agüero, and Philipp Henneke
Subjects: macrophages, immune memory, dermis, Medicine, Science, Biology (General), QH301-705.5
Abstract: Staphylococcus aureus (S. aureus) is a common colonizer of healthy skin and mucous membranes. At the same time, S. aureus is the most frequent cause of skin and soft tissue infections. Dermal macrophages (Mφ) are critical for the coordinated defense against invading S. aureus, yet they have a limited life span with replacement by bone marrow derived monocytes. It is currently poorly understood whether localized S. aureus skin infections persistently alter the resident Mφ subset composition and resistance to a subsequent infection. In a strictly dermal infection model we found that mice, which were previously infected with S. aureus, showed faster monocyte recruitment, increased bacterial killing and improved healing upon a secondary infection. However, skin infection decreased Mφ half-life, thereby limiting the duration of memory. In summary, resident dermal Mφ are programmed locally, independently of bone marrow-derived monocytes during staphylococcal skin infection leading to transiently increased resistance against a second infection.
Published: 2020
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5. Absence of gut microbiota impairs depletion of Paneth cells but not goblet cells in germ-free Atoh1lox/lox VilCreERT2 mice

Author: Mohsin Hassan, Oriol Juanola, Stefania Huber, Philipp Kellmann, Jakob Zimmermann, Edoardo Lazzarini, Stephanie C. Ganal-Vonarburg, Mercedes Gomez de Agüero, and Sheida Moghadamrad
Subjects: Hepatology, Physiology, Physiology (medical), Gastroenterology
Abstract: Cre-lox system is a powerful and widely used research tool developed to understand the specific role of genes. It allows to control the spatial and temporal expression of genes in experimental models. Several limitations including toxicity of Cre recombinase or incomplete excision of floxed loci have been reported in the past. To date, this is the first research study reporting that gut microbes also influence the expected phenotype of Paneth cell depletion in the genetically modified Math1lox/loxVilCreERT2 mouse model.
Published: 2023
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6. T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation

Author: Carolin Ulbricht, Pawel Durek, Claire Willis, Daniela Finke, Dominika W Gajdasik, Timo Rückert, Chiara Romagnani, Remi Fiancette, David R. Withers, Jakob Zimmermann, Mir-Farzin Mashreghi, Hyun-Dong Chang, Christina Stehle, and Anja E. Hauser
Subjects: Immunology, Embryogenesis, Innate lymphoid cell, chemical and pharmacologic phenomena, hemic and immune systems, Biology, Embryonic stem cell, Cell biology, medicine.anatomical_structure, Lymphatic system, RAR-related orphan receptor gamma, medicine, Immunology and Allergy, Progenitor cell, Lymph node, Transcription factor
Abstract: The generation of lymphoid tissues during embryogenesis relies on group 3 innate lymphoid cells (ILC3) displaying lymphoid tissue inducer (LTi) activity and expressing the master transcription factor RORγt. Accordingly, RORγt-deficient mice lack ILC3 and lymphoid structures, including lymph nodes (LN). Whereas T-bet affects differentiation and functions of ILC3 postnatally, the role of T-bet in regulating fetal ILC3 and LN formation remains completely unknown. Using multiple mouse models and single-cell analyses of fetal ILCs and ILC progenitors (ILCP), here we identify a key role for T-bet during embryogenesis and show that its deficiency rescues LN formation in RORγt-deficient mice. Mechanistically, T-bet deletion skews the differentiation fate of fetal ILCs and promotes the accumulation of PLZFhi ILCP expressing central LTi molecules in a RORα-dependent fashion. Our data unveil an unexpected role for T-bet and RORα during embryonic ILC function and highlight that RORγt is crucial in counteracting the suppressive effects of T-bet.
Published: 2021
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7. Counting Quasi-idempotent Irreducible Integral Matrices.

Author: Erik Thörnblad and Jakob Zimmermann
Published: 2018

8. Interleukin-22 protects intestinal stem cells against genotoxic stress

Author: Caroline Tizian, Fabian Schumacher, Konrad Gronke, Michael Kofoed-Branzk, Lukas Amann, Antigoni Triantafyllopoulou, Fabian Guendel, Mario Witkowski, Christoph S.N. Klose, Pedro P. Hernandez, Jakob Zimmermann, Hansruedi Glatt, and Andreas Diefenbach
Subjects: 0301 basic medicine, Colon, DNA repair, DNA damage, T-Lymphocytes, medicine.medical_treatment, Glucosinolates, Medizin, Apoptosis, Genotoxic Stress, Biology, Ligands, Article, Interleukin 22, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Homeostasis, Animals, ddc:610, Intestinal Mucosa, Multidisciplinary, Interleukins, Stem Cells, Innate lymphoid cell, Receptors, Interleukin, Aryl hydrocarbon receptor, Immunity, Innate, Diet, 3. Good health, Cell biology, Intestines, Cell Transformation, Neoplastic, 030104 developmental biology, Cytokine, Receptors, Aryl Hydrocarbon, 030220 oncology & carcinogenesis, Colonic Neoplasms, Mutation, biology.protein, Institut für Ernährungswissenschaft, Stem cell, DNA Damage, Mutagens
Abstract: Environmental genotoxic factors pose a challenge to the genomic integrity of epithelial cells at barrier surfaces that separate host organisms from the environment. They can induce mutations that, if they occur in epithelial stem cells, contribute to malignant transformation and cancer development1,2,3. Genome integrity in epithelial stem cells is maintained by an evolutionarily conserved cellular response pathway, the DNA damage response (DDR). The DDR culminates in either transient cell-cycle arrest and DNA repair or elimination of damaged cells by apoptosis4,5. Here we show that the cytokine interleukin-22 (IL-22), produced by group 3 innate lymphoid cells (ILC3) and γδ T cells, is an important regulator of the DDR machinery in intestinal epithelial stem cells. Using a new mouse model that enables sporadic inactivation of the IL-22 receptor in colon epithelial stem cells, we demonstrate that IL-22 is required for effective initiation of the DDR following DNA damage. Stem cells deprived of IL-22 signals and exposed to carcinogens escaped DDR-controlled apoptosis, contained more mutations and were more likely to give rise to colon cancer. We identified metabolites of glucosinolates, a group of phytochemicals contained in cruciferous vegetables, to be a widespread source of genotoxic stress in intestinal epithelial cells. These metabolites are ligands of the aryl hydrocarbon receptor (AhR)6, and AhR-mediated signalling in ILC3 and γδ T cells controlled their production of IL-22. Mice fed with diets depleted of glucosinolates produced only very low levels of IL-22 and, consequently, the DDR in epithelial cells of mice on a glucosinolate-free diet was impaired. This work identifies a homeostatic network protecting stem cells against challenge to their genome integrity by AhR-mediated ‘sensing’ of genotoxic compounds from the diet. AhR signalling, in turn, ensures on-demand production of IL-22 by innate lymphocytes directly regulating components of the DDR in epithelial stem cells.
Published: 2019
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9. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author: Lara Gibellini, Sussan Nourshargh, Susanna Cardell, Wlodzimierz Maslinski, Mar Felipo-Benavent, Florian Mair, Hans-Martin Jäck, Lilly Lopez, Klaus Warnatz, John Trowsdale, Diana Ordonez, Marcus Eich, William Hwang, Anne Cooke, Dirk Mielenz, Alberto Orfao, Winfried F. Pickl, Vladimir Benes, Alice Yue, T. Vincent Shankey, Maria Tsoumakidou, Virginia Litwin, Gelo Victoriano Dela Cruz, Andrea Cavani, Sara De Biasi, Larissa Nogueira Almeida, Jonathan J M Landry, Claudia Haftmann, Charlotte Esser, Ana Cumano, Anneke Wilharm, Francesco Dieli, Rudi Beyaert, Alessio Mazzoni, Burkhard Ludewig, Carlo Pucillo, Dirk H. Busch, Joe Trotter, Stipan Jonjić, Marc Veldhoen, Josef Spidlen, Aja M. Rieger, Dieter Adam, Srijit Khan, Todd A. Fehniger, Giuseppe Matarese, Maximilien Evrard, Christian Maueröder, Steffen Schmitt, Kristin A. Hogquist, Barry Moran, Raghavendra Palankar, Markus Feuerer, S Schmid, Susann Rahmig, Amy E. Lovett-Racke, James V. Watson, Megan K. Levings, Susanne Melzer, Dinko Pavlinic, Christopher M. Harpur, Christina Stehle, A. Graham Pockley, Toshinori Nakayama, Attila Tárnok, Juhao Yang, Michael Lohoff, Paulo Vieira, Francisco Sala-de-Oyanguren, Christian Kurts, Anastasia Gangaev, Alfonso Blanco, Hans Scherer, Regine J. Dress, Bruno Silva-Santos, Kiyoshi Takeda, Bimba F. Hoyer, Ilenia Cammarata, Daryl Grummitt, Isabel Panse, Günnur Deniz, Bianka Baying, Friederike Ebner, Esther Schimisky, Leo Hansmann, Thomas Kamradt, Edwin van der Pol, Daniel Scott-Algara, Anna Iannone, Giorgia Alvisi, Sebastian R. Schulz, Francesco Liotta, Irmgard Förster, Beatriz Jávega, Hans-Peter Rahn, Caetano Reis e Sousa, Livius Penter, Xuetao Cao, David P. Sester, Keisuke Goda, Peter Wurst, Iain B. McInnes, Ricardo T. Gazzinelli, Federica Piancone, Gerald Willimsky, Yotam Raz, Pärt Peterson, Wolfgang Fritzsche, Yvonne Samstag, Martin Büscher, Thomas Schüler, Susanne Hartmann, Robert J. Wilkinson, Anna E. S. Brooks, Steven L. C. Ketelaars, Catherine Sautès-Fridman, Anna Rubartelli, Petra Bacher, Katja Kobow, Marco A. Cassatella, Andrea Hauser, Henrik E. Mei, Kilian Schober, Silvia Della Bella, Graham Anderson, Michael D. Ward, Garth Cameron, Sebastian Lunemann, Katharina Kriegsmann, Katarzyna M. Sitnik, Brice Gaudilliere, Chantip Dang-Heine, Marcello Pinti, Paul Klenerman, Frank A. Schildberg, Joana Barros-Martins, Laura G. Rico, Hanlin Zhang, Christian Münz, Thomas Dörner, Jakob Zimmermann, Andrea M. Cooper, Jonni S. Moore, Andreas Diefenbach, Yanling Liu, Wolfgang Bauer, Tobit Steinmetz, Katharina Pracht, Leonard Tan, Peter K. Jani, Alan M. Stall, Petra Hoffmann, Christine S. Falk, Jasmin Knopf, Simon Fillatreau, Hans-Dieter Volk, Luis E. Muñoz, David L. Haviland, William W. Agace, Jonathan Rebhahn, Ljiljana Cvetkovic, Mohamed Trebak, Jordi Petriz, Mario Clerici, Diether J. Recktenwald, Anders Ståhlberg, Tristan Holland, Helen M. McGuire, Sa A. Wang, Christian Kukat, Thomas Kroneis, Laura Cook, Wan Ting Kong, Xin M. Wang, Britta Engelhardt, Pierre Coulie, Genny Del Zotto, Sally A. Quataert, Kata Filkor, Gabriele Multhoff, Bartek Rajwa, Federica Calzetti, Hans Minderman, Cosima T. Baldari, Jens Geginat, Hervé Luche, Gert Van Isterdael, Linda Schadt, Sophia Urbanczyk, Giovanna Borsellino, Liping Yu, Dale I. Godfrey, Achille Anselmo, Rachael C. Walker, Andreas Grützkau, David W. Hedley, Birgit Sawitzki, Silvia Piconese, Maria Yazdanbakhsh, Burkhard Becher, Ramon Bellmas Sanz, Michael Delacher, Hyun-Dong Chang, Immanuel Andrä, Hans-Gustaf Ljunggren, José-Enrique O'Connor, Ahad Khalilnezhad, Sharon Sanderson, Federico Colombo, Götz R. A. Ehrhardt, Inga Sandrock, Enrico Lugli, Christian Bogdan, James B. Wing, Susann Müller, Tomohiro Kurosaki, Derek Davies, Ester B. M. Remmerswaal, Kylie M. Quinn, Christopher A. Hunter, Andreas Radbruch, Timothy P. Bushnell, Anna Erdei, Sabine Adam-Klages, Pascale Eede, Van Duc Dang, Rieke Winkelmann, Thomas Korn, Gemma A. Foulds, Dirk Baumjohann, Matthias Schiemann, Manfred Kopf, Jan Kisielow, Lisa Richter, Jochen Huehn, Gloria Martrus, Alexander Scheffold, Jessica G. Borger, Sidonia B G Eckle, John Bellamy Foster, Anna Katharina Simon, Alicia Wong, Mübeccel Akdis, Gisa Tiegs, Toralf Kaiser, James McCluskey, Anna Vittoria Mattioli, Aaron J. Marshall, Hui-Fern Koay, Eva Orlowski-Oliver, Anja E. Hauser, J. Paul Robinson, Jay K. Kolls, Luca Battistini, Mairi McGrath, Jane L. Grogan, Natalio Garbi, Timothy Tree, Kingston H. G. Mills, Stefan H. E. Kaufmann, Wolfgang Schuh, Ryan R. Brinkman, Tim R. Mosmann, Vincenzo Barnaba, Andreas Dolf, Lorenzo Cosmi, Bo Huang, Andreia C. Lino, Baerbel Keller, René A. W. van Lier, Alexandra J. Corbett, Paul S. Frenette, Pleun Hombrink, Helena Radbruch, Sofie Van Gassen, Olivier Lantz, Lorenzo Moretta, Désirée Kunkel, Kirsten A. Ward-Hartstonge, Armin Saalmüller, Leslie Y. T. Leung, Salvador Vento-Asturias, Paola Lanuti, Alicia Martínez-Romero, Sarah Warth, Zhiyong Poon, Diana Dudziak, Andrea Cossarizza, Kovit Pattanapanyasat, Konrad von Volkmann, Jessica P. Houston, Agnès Lehuen, Andrew Filby, Pratip K. Chattopadhyay, Stefano Casola, Annika Wiedemann, Hannes Stockinger, Jürgen Ruland, Arturo Zychlinsky, Claudia Waskow, Katrin Neumann, Ari Waisman, Lucienne Chatenoud, Sudipto Bari, Kamran Ghoreschi, David W. Galbraith, Yvan Saeys, Hamida Hammad, Andrea Gori, Miguel López-Botet, Gabriel Núñez, Sabine Ivison, Michael Hundemer, Dorothea Reimer, Mark C. Dessing, Günter J. Hämmerling, Rudolf A. Manz, Tomas Kalina, Jonas Hahn, Holden T. Maecker, Hendy Kristyanto, Martin S. Davey, Henning Ulrich, Michael L. Dustin, Takashi Saito, Yousuke Takahama, Milena Nasi, Johanna Huber, Jürgen Wienands, Paolo Dellabona, Andreas Schlitzer, Michael D. Leipold, Kerstin H. Mair, Christian Peth, Immo Prinz, Chiara Romagnani, José M. González-Navajas, Josephine Schlosser, Marina Saresella, Matthias Edinger, Dirk Brenner, Nicole Baumgarth, Rikard Holmdahl, Fang-Ping Huang, Guadalupe Herrera, Malte Paulsen, Gergely Toldi, Luka Cicin-Sain, Reiner Schulte, Christina E. Zielinski, Thomas Winkler, Christoph Goettlinger, Philip E. Boulais, Jennie H M Yang, Antonio Celada, Heike Kunze-Schumacher, Julia Tornack, Florian Ingelfinger, Jenny Mjösberg, Andy Riddell, Leonie Wegener, Thomas Höfer, Christoph Hess, James P. Di Santo, Anna E. Oja, J. Kühne, Willem van de Veen, Mary Bebawy, Alberto Mantovani, Bart Everts, Giovanna Lombardi, Laura Maggi, Anouk von Borstel, Pia Kvistborg, Elisabetta Traggiai, A Ochel, Nima Aghaeepour, Charles-Antoine Dutertre, Matthieu Allez, Thomas Höllt, Wenjun Ouyang, Regina Stark, Maries van den Broek, Shimon Sakaguchi, Paul K. Wallace, Silvano Sozzani, Francesca LaRosa, Annette Oxenius, Malgorzata J. Podolska, Ivana Marventano, Wilhelm Gerner, Oliver F. Wirz, Britta Frehse, Gevitha Ravichandran, Martin Herrmann, Carl S. Goodyear, Gary Warnes, Helen Ferry, Stefan Frischbutter, Tim R. Radstake, Salomé LeibundGut-Landmann, Yi Zhao, Axel Schulz, Angela Santoni, Pablo Engel, Daniela C. Hernández, Andreas Acs, Cristiano Scottà, Francesco Annunziato, Thomas Weisenburger, Wolfgang Beisker, Sue Chow, Fritz Melchers, Daniel E. Speiser, Immanuel Kwok, Florent Ginhoux, Dominic A. Boardman, Natalie Stanley, Carsten Watzl, Marie Follo, Erik Lubberts, Andreas Krueger, Susanne Ziegler, Göran K. Hansson, David Voehringer, Antonia Niedobitek, Eleni Christakou, Lai Guan Ng, Sabine Baumgart, Nicholas A Gherardin, Antonio Cosma, Orla Maguire, Jolene Bradford, Daniel Schraivogel, Linda Quatrini, Stephen D. Miller, Rheumatology, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Institute of Clinical Molecular Biology, Kiel University, Department of Life Sciences [Siena, Italy], Università degli Studi di Siena = University of Siena (UNISI), Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Dulbecco Telethon Institute/Department of Biology, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, European Molecular Biology Laboratory [Heidelberg] (EMBL), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Fondazione Santa Lucia (IRCCS), Department of Immunology, Chinese Academy of Medical Sciences, FIRC Institute of Molecular Oncology Foundation, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiopatology and Transplantation, University of Milan (DEPT), University of Milan, Monash University [Clayton], Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute of Cellular Pathology, Université Catholique de Louvain = Catholic University of Louvain (UCL), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biopharmacy [Bruxelles, Belgium] (Institute for Medical Immunology IMI), Université libre de Bruxelles (ULB), Charité Hospital, Humboldt-Universität zu Berlin, Agency for science, technology and research [Singapore] (A*STAR), Laboratory of Molecular Immunology and the Howard Hughes Institute, Rockefeller University [New York], Kennedy Institute of Rheumatology [Oxford, UK], Imperial College London, Theodor Kocher Institute, University of Bern, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] ( IUF), Université Lumière - Lyon 2 (UL2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Edinburgh, Integrative Biology Program [Milano], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Universitat de Barcelona (UB), Rheumatologie, Cell Biology, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department for Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Delft University of Technology (TU Delft), Medical Inflammation Research, Karolinska Institutet [Stockholm], Department of Photonics Engineering [Lyngby], Technical University of Denmark [Lyngby] (DTU), Dpt of Experimental Immunology [Braunschweig], Helmholtz Centre for Infection Research (HZI), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Histology and Embryology, University of Rijeka, Freiburg University Medical Center, Nuffield Dept of Clinical Medicine, University of Oxford [Oxford]-NIHR Biomedical Research Centre, Institute of Integrative Biology, Molecular Biomedicine, Berlin Institute of Health (BIH), Laboratory for Lymphocyte Differentiation, RIKEN Research Center, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Department of Surgery [Vancouver, BC, Canada] (Child and Family Research Institute), University of British Columbia (UBC)-Child and Family Research Institute [Vancouver, BC, Canada], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, King‘s College London, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brustzentrum Kantonsspital St. Gallen, Immunotechnology Section, Vaccine Research Center, National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Diseases, Heinrich Pette Institute [Hamburg], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Immunology and Cell Biology, Mario Negri Institute, Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation, Institute of Translational Medicine, Klinik für Dermatologie, Venerologie und Allergologie, School of Biochemistry and Immunology, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Centre de Recherche Publique- Santé, Université du Luxembourg (Uni.lu), William Harvey Research Institute, Barts and the London Medical School, University of Michigan [Ann Arbor], University of Michigan System, Centro de Investigacion del Cancer (CSIC), Universitario de Salamanca, Molecular Pathology [Tartu, Estonia], University of Tartu, Hannover Medical School [Hannover] (MHH), Centre d'Immunologie de Marseille - Luminy (CIML), Monash Biomedicine Discovery Institute, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Data Mining and Modelling for Biomedicine [Ghent, Belgium], VIB Center for Inflammation Research [Ghent, Belgium], Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, RIKEN Research Center for Allergy and Immunology, Osaka University [Osaka], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institute of Medical Immunology [Berlin, Germany], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Otto-von-Guericke University [Magdeburg] (OVGU), SUPA School of Physics and Astronomy [University of St Andrews], University of St Andrews [Scotland]-Scottish Universities Physics Alliance (SUPA), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), General Pathology and Immunology (GPI), University of Brescia, Université de Lausanne (UNIL), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Dept. Pediatric Cardiology, Universität Leipzig [Leipzig], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Cardiovascular Sciences, Albany Medical College, Dept Pathol, Div Immunol, University of Cambridge [UK] (CAM), Department of Information Technology [Gent], Universiteit Gent, Department of Plant Systems Biology, Department of Plant Biotechnology and Genetics, Universiteit Gent = Ghent University [Belgium] (UGENT), Division of Molecular Immunology, Institute for Immunology, Department of Geological Sciences, University of Oregon [Eugene], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, University of Colorado [Colorado Springs] (UCCS), FACS laboratory, Cancer Research, London, Cancer Research UK, Regeneration in Hematopoiesis and Animal Models of Hematopoiesis, Faculty of Medicine, Dresden University of Technology, Barbara Davis Center for Childhood Diabetes (BDC), University of Colorado Anschutz [Aurora], School of Computer and Electronic Information [Guangxi University], Guangxi University [Nanning], School of Materials Science and Engineering, Nanyang Technological University [Singapour], Max Planck Institute for Infection Biology (MPIIB), Max-Planck-Gesellschaft, Work in the laboratory of Dieter Adam is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 125440785 – SFB 877, Project B2.Petra Hoffmann, Andrea Hauser, and Matthias Edinger thank BD Biosciences®, San José, CA, USA, and SKAN AG, Bale, Switzerland for fruitful cooperation during the development, construction, and installation of the GMP‐compliant cell sorting equipment and the Bavarian Immune Therapy Network (BayImmuNet) for financial support.Edwin van der Pol and Paola Lanuti acknowledge Aleksandra Gąsecka M.D. for excellent experimental support and Dr. Rienk Nieuwland for textual suggestions. This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO‐TTW), research program VENI 15924.Jessica G Borger, Kylie M Quinn, Mairi McGrath, and Regina Stark thank Francesco Siracusa and Patrick Maschmeyer for providing data.Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14‐1. Rudolf A. Manz was supported by the Excellence Cluster 'Inflammation at Interfaces' (EXC 306/2).Susanne Hartmann and Friederike Ebner were supported by the German Research Foundation (GRK 2046).Hans Minderman was supported by NIH R50CA211108.This work was funded by the Deutsche Forschungsgemeinschaft through the grant TRR130 (project P11 and C03) to Thomas H. Winkler.Ramon Bellmàs Sanz, Jenny Kühne, and Christine S. Falk thank Jana Keil and Kerstin Daemen for excellent technical support. The work was funded by the Germany Research Foundation CRC738/B3 (CSF).The work by the Mei laboratory was supported by German Research Foundation Grant ME 3644/5‐1 and TRR130 TP24, the German Rheumatism Research Centre Berlin, European Union Innovative Medicines Initiative ‐ Joint Undertaking ‐ RTCure Grant Agreement 777357, the Else Kröner‐Fresenius‐Foundation, German Federal Ministry of Education and Research e:Med sysINFLAME Program Grant 01ZX1306B and KMU‐innovativ 'InnoCyt', and the Leibniz Science Campus for Chronic Inflammation (http://www.chronische-entzuendung.org).Axel Ronald Schulz, Antonio Cosma, Sabine Baumgart, Brice Gaudilliere, Helen M. McGuire, and Henrik E. Mei thank Michael D. Leipold for critically reading the manuscript.Christian Kukat acknowledges support from the ISAC SRL Emerging Leaders program.John Trowsdale received funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant Agreement 695551)., European Project: 7728036(1978), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Università degli Studi di Milano = University of Milan (UNIMI), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] (IUF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universität Heidelberg [Heidelberg] = Heidelberg University, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), University of Oxford-NIHR Biomedical Research Centre, Universität Bonn = University of Bonn, Università degli Studi di Firenze = University of Florence (UniFI), Università degli studi di Genova = University of Genoa (UniGe), Universidad de Salamanca, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Université de Lausanne = University of Lausanne (UNIL), Universität Leipzig, Universiteit Gent = Ghent University (UGENT), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., Cossarizza, A., Chang, H. -D., Radbruch, A., Acs, A., Adam, D., Adam-Klages, S., Agace, W. W., Aghaeepour, N., Akdis, M., Allez, M., Almeida, L. N., Alvisi, G., Anderson, G., Andra, I., Annunziato, F., Anselmo, A., Bacher, P., Baldari, C. T., Bari, S., Barnaba, V., Barros-Martins, J., Battistini, L., Bauer, W., Baumgart, S., Baumgarth, N., Baumjohann, D., Baying, B., Bebawy, M., Becher, B., Beisker, W., Benes, V., Beyaert, R., Blanco, A., Boardman, D. A., Bogdan, C., Borger, J. G., Borsellino, G., Boulais, P. E., Bradford, J. A., Brenner, D., Brinkman, R. R., Brooks, A. E. S., Busch, D. H., Buscher, M., Bushnell, T. P., Calzetti, F., Cameron, G., Cammarata, I., Cao, X., Cardell, S. L., Casola, S., Cassatella, M. A., Cavani, A., Celada, A., Chatenoud, L., Chattopadhyay, P. K., Chow, S., Christakou, E., Cicin-Sain, L., Clerici, M., Colombo, F. S., Cook, L., Cooke, A., Cooper, A. M., Corbett, A. J., Cosma, A., Cosmi, L., Coulie, P. G., Cumano, A., Cvetkovic, L., Dang, V. D., Dang-Heine, C., Davey, M. S., Davies, D., De Biasi, S., Del Zotto, G., Dela Cruz, G. V., Delacher, M., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Di Santo, J. P., Diefenbach, A., Dieli, F., Dolf, A., Dorner, T., Dress, R. J., Dudziak, D., Dustin, M., Dutertre, C. -A., Ebner, F., Eckle, S. B. G., Edinger, M., Eede, P., Ehrhardt, G. R. A., Eich, M., Engel, P., Engelhardt, B., Erdei, A., Esser, C., Everts, B., Evrard, M., Falk, C. S., Fehniger, T. A., Felipo-Benavent, M., Ferry, H., Feuerer, M., Filby, A., Filkor, K., Fillatreau, S., Follo, M., Forster, I., Foster, J., Foulds, G. A., Frehse, B., Frenette, P. S., Frischbutter, S., Fritzsche, W., Galbraith, D. W., Gangaev, A., Garbi, N., Gaudilliere, B., Gazzinelli, R. T., Geginat, J., Gerner, W., Gherardin, N. A., Ghoreschi, K., Gibellini, L., Ginhoux, F., Goda, K., Godfrey, D. I., Goettlinger, C., Gonzalez-Navajas, J. M., Goodyear, C. S., Gori, A., Grogan, J. L., Grummitt, D., Grutzkau, A., Haftmann, C., Hahn, J., Hammad, H., Hammerling, G., Hansmann, L., Hansson, G., Harpur, C. M., Hartmann, S., Hauser, A., Hauser, A. E., Haviland, D. L., Hedley, D., Hernandez, D. C., Herrera, G., Herrmann, M., Hess, C., Hofer, T., Hoffmann, P., Hogquist, K., Holland, T., Hollt, T., Holmdahl, R., Hombrink, P., Houston, J. P., Hoyer, B. F., Huang, B., Huang, F. -P., Huber, J. E., Huehn, J., Hundemer, M., Hunter, C. A., Hwang, W. Y. K., Iannone, A., Ingelfinger, F., Ivison, S. M., Jack, H. -M., Jani, P. K., Javega, B., Jonjic, S., Kaiser, T., Kalina, T., Kamradt, T., Kaufmann, S. H. E., Keller, B., Ketelaars, S. L. C., Khalilnezhad, A., Khan, S., Kisielow, J., Klenerman, P., Knopf, J., Koay, H. -F., Kobow, K., Kolls, J. K., Kong, W. T., Kopf, M., Korn, T., Kriegsmann, K., Kristyanto, H., Kroneis, T., Krueger, A., Kuhne, J., Kukat, C., Kunkel, D., Kunze-Schumacher, H., Kurosaki, T., Kurts, C., Kvistborg, P., Kwok, I., Landry, J., Lantz, O., Lanuti, P., Larosa, F., Lehuen, A., LeibundGut-Landmann, S., Leipold, M. D., Leung, L. Y. T., Levings, M. K., Lino, A. C., Liotta, F., Litwin, V., Liu, Y., Ljunggren, H. -G., Lohoff, M., Lombardi, G., Lopez, L., Lopez-Botet, M., Lovett-Racke, A. E., Lubberts, E., Luche, H., Ludewig, B., Lugli, E., Lunemann, S., Maecker, H. T., Maggi, L., Maguire, O., Mair, F., Mair, K. H., Mantovani, A., Manz, R. A., Marshall, A. J., Martinez-Romero, A., Martrus, G., Marventano, I., Maslinski, W., Matarese, G., Mattioli, A. V., Maueroder, C., Mazzoni, A., Mccluskey, J., Mcgrath, M., Mcguire, H. M., Mcinnes, I. B., Mei, H. E., Melchers, F., Melzer, S., Mielenz, D., Miller, S. D., Mills, K. H. G., Minderman, H., Mjosberg, J., Moore, J., Moran, B., Moretta, L., Mosmann, T. R., Muller, S., Multhoff, G., Munoz, L. E., Munz, C., Nakayama, T., Nasi, M., Neumann, K., Ng, L. G., Niedobitek, A., Nourshargh, S., Nunez, G., O'Connor, J. -E., Ochel, A., Oja, A., Ordonez, D., Orfao, A., Orlowski-Oliver, E., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Pattanapanyasat, K., Paulsen, M., Pavlinic, D., Penter, L., Peterson, P., Peth, C., Petriz, J., Piancone, F., Pickl, W. F., Piconese, S., Pinti, M., Pockley, A. G., Podolska, M. J., Poon, Z., Pracht, K., Prinz, I., Pucillo, C. E. M., Quataert, S. A., Quatrini, L., Quinn, K. M., Radbruch, H., Radstake, T. R. D. J., Rahmig, S., Rahn, H. -P., Rajwa, B., Ravichandran, G., Raz, Y., Rebhahn, J. A., Recktenwald, D., Reimer, D., Reis e Sousa, C., Remmerswaal, E. B. M., Richter, L., Rico, L. G., Riddell, A., Rieger, A. M., Robinson, J. P., Romagnani, C., Rubartelli, A., Ruland, J., Saalmuller, A., Saeys, Y., Saito, T., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sandrock, I., Santoni, A., Sanz, R. B., Saresella, M., Sautes-Fridman, C., Sawitzki, B., Schadt, L., Scheffold, A., Scherer, H. U., Schiemann, M., Schildberg, F. A., Schimisky, E., Schlitzer, A., Schlosser, J., Schmid, S., Schmitt, S., Schober, K., Schraivogel, D., Schuh, W., Schuler, T., Schulte, R., Schulz, A. R., Schulz, S. R., Scotta, C., Scott-Algara, D., Sester, D. P., Shankey, T. V., Silva-Santos, B., Simon, A. K., Sitnik, K. M., Sozzani, S., Speiser, D. E., Spidlen, J., Stahlberg, A., Stall, A. M., Stanley, N., Stark, R., Stehle, C., Steinmetz, T., Stockinger, H., Takahama, Y., Takeda, K., Tan, L., Tarnok, A., Tiegs, G., Toldi, G., Tornack, J., Traggiai, E., Trebak, M., Tree, T. I. M., Trotter, J., Trowsdale, J., Tsoumakidou, M., Ulrich, H., Urbanczyk, S., van de Veen, W., van den Broek, M., van der Pol, E., Van Gassen, S., Van Isterdael, G., van Lier, R. A. W., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H. -D., von Borstel, A., von Volkmann, K., Waisman, A., Walker, R. V., Wallace, P. K., Wang, S. A., Wang, X. M., Ward, M. D., Ward-Hartstonge, K. A., Warnatz, K., Warnes, G., Warth, S., Waskow, C., Watson, J. V., Watzl, C., Wegener, L., Weisenburger, T., Wiedemann, A., Wienands, J., Wilharm, A., Wilkinson, R. J., Willimsky, G., Wing, J. B., Winkelmann, R., Winkler, T. H., Wirz, O. F., Wong, A., Wurst, P., Yang, J. H. M., Yang, J., Yazdanbakhsh, M., Yu, L., Yue, A., Zhang, H., Zhao, Y., Ziegler, S. M., Zielinski, C., Zimmermann, J., Zychlinsky, A., UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/GECE - Génétique cellulaire, Netherlands Organization for Scientific Research, German Research Foundation, European Commission, European Research Council, Repositório da Universidade de Lisboa, CCA - Imaging and biomarkers, Experimental Immunology, AII - Infectious diseases, AII - Inflammatory diseases, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, and Landsteiner Laboratory
Subjects: 0301 basic medicine, Consensus, Immunology, Consensu, Cell Separation, Biology, Article, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Guidelines, Allergy and Immunology, medicine, Cell separation, Immunology and Allergy, Humans, guidelines, flow cytometry, immunology, medicine.diagnostic_test, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Cell sorting, Flow Cytometry, Cell selection, Data science, 3. Good health, 030104 developmental biology, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, 030215 immunology, Human
Abstract: All authors: Andrea Cossarizza Hyun‐Dong Chang Andreas Radbruch Andreas Acs Dieter Adam Sabine Adam‐Klages William W. Agace Nima Aghaeepour Mübeccel Akdis Matthieu Allez Larissa Nogueira Almeida Giorgia Alvisi Graham Anderson Immanuel Andrä Francesco Annunziato Achille Anselmo Petra Bacher Cosima T. Baldari Sudipto Bari Vincenzo Barnaba Joana Barros‐Martins Luca Battistini Wolfgang Bauer Sabine Baumgart Nicole Baumgarth Dirk Baumjohann Bianka Baying Mary Bebawy Burkhard Becher Wolfgang Beisker Vladimir Benes Rudi Beyaert Alfonso Blanco Dominic A. Boardman Christian Bogdan Jessica G. Borger Giovanna Borsellino Philip E. Boulais Jolene A. Bradford Dirk Brenner Ryan R. Brinkman Anna E. S. Brooks Dirk H. Busch Martin Büscher Timothy P. Bushnell Federica Calzetti Garth Cameron Ilenia Cammarata Xuetao Cao Susanna L. Cardell Stefano Casola Marco A. Cassatella Andrea Cavani Antonio Celada Lucienne Chatenoud Pratip K. Chattopadhyay Sue Chow Eleni Christakou Luka Čičin‐Šain Mario Clerici Federico S. Colombo Laura Cook Anne Cooke Andrea M. Cooper Alexandra J. Corbett Antonio Cosma Lorenzo Cosmi Pierre G. Coulie Ana Cumano Ljiljana Cvetkovic Van Duc Dang Chantip Dang‐Heine Martin S. Davey Derek Davies Sara De Biasi Genny Del Zotto Gelo Victoriano Dela Cruz Michael Delacher Silvia Della Bella Paolo Dellabona Günnur Deniz Mark Dessing James P. Di Santo Andreas Diefenbach Francesco Dieli Andreas Dolf Thomas Dörner Regine J. Dress Diana Dudziak Michael Dustin Charles‐Antoine Dutertre Friederike Ebner Sidonia B. G. Eckle Matthias Edinger Pascale Eede Götz R.A. Ehrhardt Marcus Eich Pablo Engel Britta Engelhardt Anna Erdei Charlotte Esser Bart Everts Maximilien Evrard Christine S. Falk Todd A. Fehniger Mar Felipo‐Benavent Helen Ferry Markus Feuerer Andrew Filby Kata Filkor Simon Fillatreau Marie Follo Irmgard Förster John Foster Gemma A. Foulds Britta Frehse Paul S. Frenette Stefan Frischbutter Wolfgang Fritzsche David W. Galbraith Anastasia Gangaev Natalio Garbi Brice Gaudilliere Ricardo T. Gazzinelli Jens Geginat Wilhelm Gerner Nicholas A. Gherardin Kamran Ghoreschi Lara Gibellini Florent Ginhoux Keisuke Goda Dale I. Godfrey Christoph Goettlinger Jose M. González‐Navajas Carl S. Goodyear Andrea Gori Jane L. Grogan Daryl Grummitt Andreas Grützkau Claudia Haftmann Jonas Hahn Hamida Hammad Günter Hämmerling Leo Hansmann Goran Hansson Christopher M. Harpur Susanne Hartmann Andrea Hauser Anja E. Hauser David L. Haviland David Hedley Daniela C. Hernández Guadalupe Herrera Martin Herrmann Christoph Hess Thomas Höfer Petra Hoffmann Kristin Hogquist Tristan Holland Thomas Höllt Rikard Holmdahl Pleun Hombrink Jessica P. Houston Bimba F. Hoyer Bo Huang Fang‐Ping Huang Johanna E. Huber Jochen Huehn Michael Hundemer Christopher A. Hunter William Y. K. Hwang Anna Iannone Florian Ingelfinger Sabine M Ivison Hans‐Martin Jäck Peter K. Jani Beatriz Jávega Stipan Jonjic Toralf Kaiser Tomas Kalina Thomas Kamradt Stefan H. E. Kaufmann Baerbel Keller Steven L. C. Ketelaars Ahad Khalilnezhad Srijit Khan Jan Kisielow Paul Klenerman Jasmin Knopf Hui‐Fern Koay Katja Kobow Jay K. Kolls Wan Ting Kong Manfred Kopf Thomas Korn Katharina Kriegsmann Hendy Kristyanto Thomas Kroneis Andreas Krueger Jenny Kühne Christian Kukat Désirée Kunkel Heike Kunze‐Schumacher Tomohiro Kurosaki Christian Kurts Pia Kvistborg Immanuel Kwok Jonathan Landry Olivier Lantz Paola Lanuti Francesca LaRosa Agnès Lehuen Salomé LeibundGut‐Landmann Michael D. Leipold Leslie Y.T. Leung Megan K. Levings Andreia C. Lino Francesco Liotta Virginia Litwin Yanling Liu Hans‐Gustaf Ljunggren Michael Lohoff Giovanna Lombardi Lilly Lopez Miguel López‐Botet Amy E. Lovett‐Racke Erik Lubberts Herve Luche Burkhard Ludewig Enrico Lugli Sebastian Lunemann Holden T. Maecker Laura Maggi Orla Maguire Florian Mair Kerstin H. Mair Alberto Mantovani Rudolf A. Manz Aaron J. Marshall Alicia Martínez‐Romero Glòria Martrus Ivana Marventano Wlodzimierz Maslinski Giuseppe Matarese Anna Vittoria Mattioli Christian Maueröder Alessio Mazzoni James McCluskey Mairi McGrath Helen M. McGuire Iain B. McInnes Henrik E. Mei Fritz Melchers Susanne Melzer Dirk Mielenz Stephen D. Miller Kingston H.G. Mills Hans Minderman Jenny Mjösberg Jonni Moore Barry Moran Lorenzo Moretta Tim R. Mosmann Susann Müller Gabriele Multhoff Luis Enrique Muñoz Christian Münz Toshinori Nakayama Milena Nasi Katrin Neumann Lai Guan Ng Antonia Niedobitek Sussan Nourshargh Gabriel Núñez José‐Enrique O'Connor Aaron Ochel Anna Oja Diana Ordonez Alberto Orfao Eva Orlowski‐Oliver Wenjun Ouyang Annette Oxenius Raghavendra Palankar Isabel Panse Kovit Pattanapanyasat Malte Paulsen Dinko Pavlinic Livius Penter Pärt Peterson Christian Peth Jordi Petriz Federica Piancone Winfried F. Pickl Silvia Piconese Marcello Pinti A. Graham Pockley Malgorzata Justyna Podolska Zhiyong Poon Katharina Pracht Immo Prinz Carlo E. M. Pucillo Sally A. Quataert Linda Quatrini Kylie M. Quinn Helena Radbruch Tim R. D. J. Radstake Susann Rahmig Hans‐Peter Rahn Bartek Rajwa Gevitha Ravichandran Yotam Raz Jonathan A. Rebhahn Diether Recktenwald Dorothea Reimer Caetano Reis e Sousa Ester B.M. Remmerswaal Lisa Richter Laura G. Rico Andy Riddell Aja M. Rieger J. Paul Robinson Chiara Romagnani Anna Rubartelli Jürgen Ruland Armin Saalmüller Yvan Saeys Takashi Saito Shimon Sakaguchi Francisco Sala‐de‐Oyanguren Yvonne Samstag Sharon Sanderson Inga Sandrock Angela Santoni Ramon Bellmàs Sanz Marina Saresella Catherine Sautes‐Fridman Birgit Sawitzki Linda Schadt Alexander Scheffold Hans U. Scherer Matthias Schiemann Frank A. Schildberg Esther Schimisky Andreas Schlitzer Josephine Schlosser Stephan Schmid Steffen Schmitt Kilian Schober Daniel Schraivogel Wolfgang Schuh Thomas Schüler Reiner Schulte Axel Ronald Schulz Sebastian R. Schulz Cristiano Scottá Daniel Scott‐Algara David P. Sester T. Vincent Shankey Bruno Silva‐Santos Anna Katharina Simon Katarzyna M. Sitnik Silvano Sozzani Daniel E. Speiser Josef Spidlen Anders Stahlberg Alan M. Stall Natalie Stanley Regina Stark Christina Stehle Tobit Steinmetz Hannes Stockinger Yousuke Takahama Kiyoshi Takeda Leonard Tan Attila Tárnok Gisa Tiegs Gergely Toldi Julia Tornack Elisabetta Traggiai Mohamed Trebak Timothy I.M. Tree Joe Trotter John Trowsdale Maria Tsoumakidou Henning Ulrich Sophia Urbanczyk Willem van de Veen Maries van den Broek Edwin van der Pol Sofie Van Gassen Gert Van Isterdael René A.W. van Lier Marc Veldhoen Salvador Vento‐Asturias Paulo Vieira David Voehringer Hans‐Dieter Volk Anouk von Borstel Konrad von Volkmann Ari Waisman Rachael V. Walker Paul K. Wallace Sa A. Wang Xin M. Wang Michael D. Ward Kirsten A Ward‐Hartstonge Klaus Warnatz Gary Warnes Sarah Warth Claudia Waskow James V. Watson Carsten Watzl Leonie Wegener Thomas Weisenburger Annika Wiedemann Jürgen Wienands Anneke Wilharm Robert John Wilkinson Gerald Willimsky James B. Wing Rieke Winkelmann Thomas H. Winkler Oliver F. Wirz Alicia Wong Peter Wurst Jennie H. M. Yang Juhao Yang Maria Yazdanbakhsh Liping Yu Alice Yue Hanlin Zhang Yi Zhao Susanne Maria Ziegler Christina Zielinski Jakob Zimmermann Arturo Zychlinsky., These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion., This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO-TTW), research program VENI 15924. This work was funded by the Deutsche Forschungsgemeinschaft. European Union Innovative Medicines Initiative - Joint Undertaking - RTCure Grant Agreement 777357 and innovation program (Grant Agreement 695551).
Published: 2019
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10. Murine T-Cell Transfer Colitis as a Model for Inflammatory Bowel Disease

Author: Patrick, Maschmeyer, Jakob, Zimmermann, and Anja Andrea, Kühl
Subjects: Homeodomain Proteins, Mice, Inbred C57BL, Mice, Knockout, Disease Models, Animal, Colon, Research Design, Animals, Cell Separation, T-Lymphocytes, Helper-Inducer, Colitis, Flow Cytometry, Adoptive Transfer, Workflow
Abstract: Inflammatory bowel disease (IBD) is a group of severe chronic inflammatory conditions of the human gastrointestinal tract. Murine models of colitis have been invaluable tools to improve the understanding of IBD development and pathogenesis. While the disease etiology of IBD is complex and multifactorial, CD4
Published: 2021

11. Evaluation of Cytokine Production at the Single Cell Level by Flow Cytometry Upon Polyclonal Stimulation

Author: Jakob, Zimmermann
Subjects: Research Design, Ionomycin, Animals, Cytokines, Humans, Tetradecanoylphorbol Acetate, T-Lymphocytes, Helper-Inducer, Single-Cell Analysis, Flow Cytometry, Cells, Cultured, Workflow
Abstract: An important hallmark for the characterisation of Th cells is their capacity for cytokine expression. In this chapter, we describe how Th cells can be restimulated polyclonally to reveal their cytokine-producing potential that can then be analysed by intracellular staining and flow cytometry.
Published: 2021

12. Long-term evolution and short-term adaptation of microbiota strains and sub-strains in mice

Author: Lars Bosshard, Bärbel Stecher, Jakob Zimmermann, Mercedes Gomez de Agüero, Bahtiyar Yilmaz, Tobias Fuhrer, Stephanie C. Ganal-Vonarburg, Wolf-Dietrich Hardt, Irene Keller, Heidi Tschanz-Lischer, Andrew J. Macpherson, Laurent Excoffier, Nerea Fernandez Trigo, Kathleen McCoy, Hai Li, Julien P. Limenitakis, Uwe Sauer, and Catherine Mooser
Subjects: Male, Silent mutation, Ralstonia, Biology, Microbiology, Mice, 03 medical and health sciences, 0302 clinical medicine, Nutrient, Virology, Animals, Metabolomics, Symbiosis, 610 Medicine & health, Gene, 030304 developmental biology, Mutualism (biology), 0303 health sciences, Bacteria, Ecotype, Microbiota, Immunity, Niche differentiation, Genomics, Adaptation, Physiological, Gastrointestinal Microbiome, Intestines, Mice, Inbred C57BL, Taxon, Evolutionary biology, 570 Life sciences, biology, Female, Parasitology, Adaptation, 030217 neurology & neurosurgery
Abstract: Isobiotic mice, with an identical stable microbiota composition, potentially allow models of host-microbial mutualism to be studied over time and between different laboratories. To understand microbiota evolution in these models, we carried out a 6-year experiment in mice colonized with 12 representative taxa. Increased non-synonymous to synonymous mutation rates indicate positive selection in multiple taxa, particularly for genes annotated for nutrient acquisition or replication. Microbial sub-strains that evolved within a single taxon can stably coexist, consistent with niche partitioning of ecotypes in the complex intestinal environment. Dietary shifts trigger rapid transcriptional adaptation to macronutrient and micronutrient changes in individual taxa and alterations in taxa biomass. The proportions of different sub-strains are also rapidly altered after dietary shift. This indicates that microbial taxa within a mouse colony adapt to changes in the intestinal environment by long-term genomic positive selection and short-term effects of transcriptional reprogramming and adjustments in sub-strain proportions. ISSN:1931-3128 ISSN:1934-6069
Published: 2021
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13. Evaluation of Cytokine Production at the Single Cell Level by Flow Cytometry Upon Polyclonal Stimulation

Author: Jakob Zimmermann
Subjects: 0301 basic medicine, medicine.diagnostic_test, biology, Chemistry, medicine.medical_treatment, fungi, food and beverages, Cytokine expression, Stimulation, Cellular level, Flow cytometry, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Cytokine, Polyclonal antibodies, Intracellular staining, medicine, biology.protein, 030215 immunology
Abstract: An important hallmark for the characterisation of Th cells is their capacity for cytokine expression. In this chapter, we describe how Th cells can be restimulated polyclonally to reveal their cytokine-producing potential that can then be analysed by intracellular staining and flow cytometry.
Published: 2021
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14. Murine T-Cell Transfer Colitis as a Model for Inflammatory Bowel Disease

Author: Anja A. Kühl, Patrick Maschmeyer, and Jakob Zimmermann
Subjects: 0301 basic medicine, Adoptive cell transfer, business.industry, T cell, Human gastrointestinal tract, T helper cell, medicine.disease, Inflammatory bowel disease, digestive system diseases, Pathogenesis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Intestinal inflammation, Immunology, medicine, 030211 gastroenterology & hepatology, Colitis, business
Abstract: Inflammatory bowel disease (IBD) is a group of severe chronic inflammatory conditions of the human gastrointestinal tract. Murine models of colitis have been invaluable tools to improve the understanding of IBD development and pathogenesis. While the disease etiology of IBD is complex and multifactorial, CD4+ T helper cells have been shown to strongly contribute to the disease pathogenesis of IBD. Here, we present a detailed protocol of the preclinical model of T-cell transfer colitis, which can easily be utilized in the laboratory to study T helper cell functions in intestinal inflammation.
Published: 2021
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15. T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation

Author: Christina, Stehle, Timo, Rückert, Rémi, Fiancette, Dominika W, Gajdasik, Claire, Willis, Carolin, Ulbricht, Pawel, Durek, Mir-Farzin, Mashreghi, Daniela, Finke, Anja Erika, Hauser, David R, Withers, Hyun-Dong, Chang, Jakob, Zimmermann, and Chiara, Romagnani
Subjects: Mice, Lymphoid Tissue, Animals, Cell Differentiation, Cell Lineage, Female, Nuclear Receptor Subfamily 1, Group F, Member 1, Lymph Nodes, Lymphocytes, T-Lymphocytes, Helper-Inducer, Nuclear Receptor Subfamily 1, Group F, Member 3, T-Box Domain Proteins, Immunity, Innate
Abstract: The generation of lymphoid tissues during embryogenesis relies on group 3 innate lymphoid cells (ILC3) displaying lymphoid tissue inducer (LTi) activity and expressing the master transcription factor RORγt. Accordingly, RORγt-deficient mice lack ILC3 and lymphoid structures, including lymph nodes (LN). Whereas T-bet affects differentiation and functions of ILC3 postnatally, the role of T-bet in regulating fetal ILC3 and LN formation remains completely unknown. Using multiple mouse models and single-cell analyses of fetal ILCs and ILC progenitors (ILCP), here we identify a key role for T-bet during embryogenesis and show that its deficiency rescues LN formation in RORγt-deficient mice. Mechanistically, T-bet deletion skews the differentiation fate of fetal ILCs and promotes the accumulation of PLZF
Published: 2020

16. Resident macrophages acquire innate immune memory in staphylococcal skin infection

Author: Florens Lohrmann, Neftali Jose Ramirez, Julia Kolter, Mercedes Gomez de Agüero, Jakob Zimmermann, Reinhild Feuerstein, Philipp Henneke, and Aaron James Forde
Subjects: Male, 0301 basic medicine, Mouse, Skin infection, medicine.disease_cause, immune memory, Monocytes, Mice, Immunology and Inflammation, 0302 clinical medicine, Biology (General), Mice, Inbred BALB C, integumentary system, General Neuroscience, General Medicine, macrophages, dermis, 3. Good health, medicine.anatomical_structure, Staphylococcus aureus, Medicine, Female, Staphylococcal Skin Infections, medicine.symptom, Research Article, QH301-705.5, Science, Secondary infection, Inflammation, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Dermis, medicine, Animals, Innate immune system, General Immunology and Microbiology, business.industry, Monocyte, medicine.disease, Immunity, Innate, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Immunology, Bone marrow, business, Immunologic Memory, 030215 immunology
Abstract: Staphylococcus aureus (S. aureus) is a common colonizer of healthy skin and mucous membranes. At the same time, S. aureus is the most frequent cause of skin and soft tissue infections. Dermal macrophages (Mφ) are critical for the coordinated defense against invading S. aureus, yet they have a limited life span with replacement by bone marrow derived monocytes. It is currently poorly understood whether localized S. aureus skin infections persistently alter the resident Mφ subset composition and resistance to a subsequent infection. In a strictly dermal infection model we found that mice, which were previously infected with S. aureus, showed faster monocyte recruitment, increased bacterial killing and improved healing upon a secondary infection. However, skin infection decreased Mφ half-life, thereby limiting the duration of memory. In summary, resident dermal Mφ are programmed locally, independently of bone marrow-derived monocytes during staphylococcal skin infection leading to transiently increased resistance against a second infection.
Published: 2020
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17. Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow

Author: Stefanie Hahne, Katrin Lehmann, Claudia Haftmann, Jannis Kummer, Melanie Weber, Silvia Kühnel, Daniel Schulz, Stefan Kröger, Ralf Köhler, Richard K. Addo, Jakob Zimmermann, Ulrike Menzel, Frederik Heinrich, Andreas Radbruch, Patrick Maschmeyer, Rebecca Cornelis, Anja E. Hauser, Sai T. Reddy, Francesco Siracusa, Gitta Anne Heinz, Ulrik Stervbo, Özen Sercan-Alp, Mir-Farzin Mashreghi, Jonathan Stefanowski, Pawel Durek, René Riedel, Hyun-Dong Chang, Victor Greiff, Marta Ferreira-Gomes, Cora Klaeden, Mairi McGrath, Kerstin Westendorf, and Sandra Naundorf
Subjects: 0301 basic medicine, General Physics and Astronomy, Immunological memory, Transcriptome, 0302 clinical medicine, 610 Medicine & health, lcsh:Science, education.field_of_study, B-Lymphocytes, Multidisciplinary, Cell Cycle, RNA sequencing, Isotype, medicine.anatomical_structure, Antibody, Stromal cell, Science, B-cell receptor, Population, Receptors, Antigen, B-Cell, Vascular Cell Adhesion Molecule-1, Spleen, Animals, Wild, Bone Marrow Cells, Mice, Transgenic, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Antibodies, 03 medical and health sciences, Antigen, Adjuvants, Immunologic, medicine, Animals, ddc:610, education, B cell, Cell Proliferation, B cells, General Chemistry, Immunoglobulin Class Switching, B-1 cell, Mice, Inbred C57BL, 030104 developmental biology, Gene Expression Regulation, Immunology, biology.protein, lcsh:Q, Bone marrow, Stromal Cells, 610 Medizin und Gesundheit, Immunologic Memory, 030215 immunology
Abstract: At present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched memory B lymphocytes (Bsm) of murine spleen and bone marrow, identified according to individual transcriptional signature and B cell receptor repertoire. A population of marginal zone-like cells is located exclusively in the spleen, while a population of quiescent Bsm is found only in the bone marrow. Three further resident populations, present in spleen and bone marrow, represent transitional and follicular B cells and B1 cells, respectively. A population representing 10-20% of spleen and bone marrow memory B cells is the only one qualifying as circulating. In the bone marrow, all cells individually dock onto VCAM1+ stromal cells and, reminiscent of resident memory T and plasma cells, are void of activation, proliferation and mobility., Nature Communications, 11 (1), ISSN:2041-1723
Published: 2020
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18. Trash Your Agar Plates! Blood Stream Bacteria Are Now Quantified by in vivo Flow Cytometry

Author: Jakob Zimmermann
Subjects: 0303 health sciences, Histology, Chromatography, Bacteria, medicine.diagnostic_test, biology, Chemistry, Cell Biology, Flow Cytometry, biology.organism_classification, Pathology and Forensic Medicine, Flow cytometry, Agar plate, Agar, 03 medical and health sciences, 0302 clinical medicine, In vivo, 030220 oncology & carcinogenesis, medicine, Humans, 570 Life sciences, Blood stream, 030304 developmental biology
Abstract: © 2020 International Society for Advancement of Cytometry.
Published: 2020
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19. Existence of symmetric maximal noncrossing collections of k-element sets

Author: Andrea Pasquali, Erik Thörnblad, and Jakob Zimmermann
Subjects: Matematik, Algebra and Number Theory, Modulo, 010102 general mathematics, 0102 computer and information sciences, 01 natural sciences, Combinatorics, symbols.namesake, 010201 computation theory & mathematics, Jacobian matrix and determinant, symbols, FOS: Mathematics, Mathematics - Combinatorics, Discrete Mathematics and Combinatorics, Combinatorics (math.CO), 0101 mathematics, Algebraic number, Invariant (mathematics), Representation Theory (math.RT), Mathematics - Representation Theory, Mathematics
Abstract: We investigate the existence of maximal collections of mutually noncrossing $k$-element subsets of $\left\{ 1, \dots, n \right\}$ that are invariant under adding $k\pmod n$ to all indices. Our main result is that such a collection exists if and only if $k$ is congruent to $0, 1$ or $-1$ modulo $n/\operatorname{GCD}(k,n)$. Moreover, we present some algebraic consequences of our result related to self-injective Jacobian algebras., Comment: 12 pages, 1 figure. Final version, to appear in Journal of Algebraic Combinatorics
Published: 2020

20. Specific microbiota enhances intestinal IgA levels by inducing TGF‐β in T follicular helper cells of Peyer's patches in mice

Author: Justus Ninnemann, René Maier, Katharina Werner, Kevin Heiking, Gitta Anne Heinz, Ute Hoffmann, Jakob Zimmermann, Alexander Beller, Britta Siegmund, Andreas Radbruch, Victoria von Goetze, René Riedel, Andrey Kruglov, Hyun-Dong Chang, Katrin Lehmann, Pawel Durek, and Mir-Farzin Mashreghi
Subjects: 0301 basic medicine, medicine.medical_treatment, Immunology, Plasma cell, 03 medical and health sciences, Mice, Peyer's Patches, 0302 clinical medicine, Follicular phase, medicine, Immunology and Allergy, Animals, Intestinal Mucosa, Gene, Immunity, Mucosal, Mice, Knockout, Mice, Inbred BALB C, biology, T-Lymphocytes, Helper-Inducer, biology.organism_classification, 3. Good health, Gastrointestinal Microbiome, Immunoglobulin A, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Immunoglobulin class switching, biology.protein, 570 Life sciences, Antibody, Bacteria, Tenericutes, 030215 immunology, Transforming growth factor
Abstract: In humans and mice, mucosal immune responses are dominated by IgA antibodies and the cytokine TGF-β, suppressing unwanted immune reactions but also targeting Ig class switching to IgA. It had been suggested that eosinophils promote the genera- tion and maintenance of mucosal IgA-expressing plasma cells. Here, we demonstrate that not eosinophils, but specific bacteria determine mucosal IgA production. Co-housing of eosinophil-deficient mice with mice having high intestinal IgA levels, as well as the intentional microbiota transfer induces TGF-β expression in intestinal T follicular helper cells, thereby promoting IgA class switching in Peyer’s patches, enhancing IgA+ plasma cell numbers in the small intestinal lamina propria and levels of mucosal IgA. We show that bacteria highly enriched for the genus Anaeroplasma are sufficient to induce these changes and enhance IgA levels when adoptively transferred. Thus, specific members of the intestinal microbiota and not the microbiota as such regulate gut homeostasis, by promoting the expression of immune-regulatory TGF-β and of mucosal IgA.
Published: 2020
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21. The intestinal microbiota determines the colitis-inducing potential of T-bet-deficient Th cells in mice

Author: Florian Schattenberg, Patrick Maschmeyer, Pawel Durek, Katrin Lehmann, René Riedel, Anja A. Kühl, Susann Müller, Andreas Radbruch, Jakob Zimmermann, Francesco Siracusa, Melanie Weber, Kerstin Westendorf, and Hyun-Dong Chang
Subjects: 0301 basic medicine, Adoptive cell transfer, Short Communication, Cellular differentiation, Immunology, 610 Medicine & health, chemical and pharmacologic phenomena, Inflammation, Biology, Lymphocyte Activation, Inflammatory bowel disease, T‐bet, Pathogenesis, Mice, T helper cells, 03 medical and health sciences, 0302 clinical medicine, Allergy and inflammation, T-Lymphocyte Subsets, medicine, Animals, Immunology and Allergy, Microbiome, Basic, Colitis, Homeodomain Proteins, Mice, Knockout, T cell transfer colitis, Microbiota, Cell Differentiation, hemic and immune systems, T-Lymphocytes, Helper-Inducer, medicine.disease, Adoptive Transfer, Gastrointestinal Microbiome, Mice, Inbred C57BL, Short Communication|Basic, Disease Models, Animal, 030104 developmental biology, 030220 oncology & carcinogenesis, T cell differentiation, medicine.symptom, T-Box Domain Proteins
Abstract: Conflicting evidence has been provided as to whether induction of intestinal inflammation by adoptive transfer of naïve T cells into Rag-/- mice requires expression of the transcription factor T-bet by the T cells. Here, we formally show that the intestinal microbiota composition of the Rag-/- recipient determines whether or not T-bet-deficient Th cells can induce colitis and we have resolved the differences of the two microbiomes, permissive or non-permissive to T-bet-independent colitis. Our data highlight the dominance of the microbiota over particular T cell differentiation programs in the pathogenesis of chronic intestinal inflammation. © 2017 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim.
Published: 2017
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22. Microbiota-gut brain axis involvement in neuropsychiatric disorders

Author: Hervé M. Blottière, Emilio Russo, Sigrid Pedersen, Francesca Ronchi, Luigi Francesco Iannone, Gaia Luongo, Federico Zara, Cinzia Ferraris, P. Mainardi, Anna Tagliabue, Alberto Preda, Gerard Clarke, Kaja Kristine Selmer, Elisa Santocchi, Stefania Provasi, Vincenzo Belcastro, Carmen Giordano, Alberto Verrotti, Pietro Baldelli, Carlo Minetti, Rita Citraro, Diego Albani, Pasquale Striano, Andrea Petretto, Paola Iannetti, Marco Carotenuto, Jakob Zimmermann, Nicola Segata, Annamaria Cattaneo, Alberto Spalice, Letizia Guiducci, Sanjay M. Sisodiya, Iannone, Luigi Francesco, Preda, Alberto, Blottière, Hervé M, Clarke, Gerard, Albani, Diego, Belcastro, Vincenzo, Carotenuto, Marco, Cattaneo, Annamaria, Citraro, Rita, Ferraris, Cinzia, Ronchi, Francesca, Luongo, Gaia, Santocchi, Elisa, Guiducci, Letizia, Baldelli, Pietro, Iannetti, Paola, Pedersen, Sigrid, Petretto, Andrea, Provasi, Stefania, Selmer, Kaja, Spalice, Alberto, Tagliabue, Anna, Verrotti, Alberto, Segata, Nicola, Zimmermann, Jakob, Minetti, Carlo, Mainardi, Paolo, Giordano, Carmen, Sisodiya, Sanjay, Zara, Federico, Russo, Emilio, Striano, Pasquale, University of Catanzaro, University of Genoa (UNIGE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, University College Cork (UCC), IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Saint Anna Hospital, Partenaires INRAE, Università degli studi della Campania 'Luigi Vanvitelli', King's College, University of Pavia, University of Bern, Ordine dei Tecnologi Alimentari Campania e Lazio, Stella Maris Foundation, Institute of Clinical Physiology, National Council of Research, University of Genova, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Oslo University Hospital [Oslo], Istituto Giannina Gaslini, University of Laquila, University of Trento, Kolfarma SRL, Department of Chemistry, Materials and Chemical Engineering 'Giulio Natta' (CMIC), Politecnico di Milano [Milan] (POLIMI), Department of Clinical and Experimental Epilepsy, and UCL Institute of Neurology
Subjects: microbiota-gut brain axis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Central nervous system, Gut–brain axis, Inflammation, Bidirectional communication, digestive system, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, Ketogenic diet, inflammation, manipulating microbiota, metabolomics, neuropsychiatric disorders, Central Nervous System Diseases, medicine, microbiota-gut brain axi, Humans, Pharmacology (medical), Ketogenic diet, inflammation, manipulating microbiota, metabolomics, microbiota-gut brain axis, neuropsychiatric disorders, business.industry, General Neuroscience, Multiple sclerosis, Mental Disorders, medicine.disease, 3. Good health, 030227 psychiatry, Clinical neurology, Gastrointestinal Microbiome, stomatognathic diseases, medicine.anatomical_structure, Clinical evidence, Immunology, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, metabolomic
Abstract: International audience; Introduction: The microbiota-gut brain (MGB) axis is the bidirectional communication between the intestinal microbiota and the brain. An increasing body of preclinical and clinical evidence has revealed that the gut microbial ecosystem can affect neuropsychiatric health. However, there is still a need of further studies to elucidate the complex gene-environment interactions and the role of the MGB axis in neuropsychiatric diseases, with the aim of identifying biomarkers and new therapeutic targets, to allow early diagnosis and improving treatments. Areas covered: To review the role of MGB axis in neuropsychiatric disorders, prediction and prevention of disease through exploitation, integration, and combination of data from existing gut microbiome/microbiota projects and appropriate other International '-Omics' studies. The authors also evaluated the new technological advances to investigate and modulate, through nutritional and other interventions, the gut microbiota. Expert opinion: The clinical studies have documented an association between alterations in gut microbiota composition and/or function, whereas the preclinical studies support a role for the gut microbiota in impacting behaviors which are of relevance to psychiatry and other central nervous system (CNS) disorders. Targeting MGB axis could be an additional approach for treating CNS disorders and all conditions in which alterations of the gut microbiota are involved.
Published: 2019
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23. Development of a Manufacturing Process for Polyimide-Based Microstructured Devices Using Reactive Ion Etching

Author: Arndt-Christian Schneider, Jens Bobers, Norbert Kockmann, Jakob Zimmermann, and Maurice Hesselmann
Subjects: Rapid prototyping, Materials science, Manufacturing process, Etching (microfabrication), Nanotechnology, Reactive-ion etching, Polyimide
Abstract: Miniaturization and modularization are fast growing fields in chemical engineering in recent years. Fast and flexible production processes for microstructured devices are desirable to meet the requirements of rapid prototyping and flexible chip manufacturing. Reactive ion etching provides a structuring process which leads to a highly precise and anisotropic etching behavior. A new manufacturing process for polyimide-based microstructured devices with low surface roughness was developed and applied on reactor geometry for liquid-liquid two-phase-flow. The fabricated chip geometry is designed for creating droplets via flow focusing as the dispersed phase is incised by two continuous phase inlet streams. The droplets are created in the widening channel. In order to keep the pressure loss for the developed reactor geometry and the production time as small as possible, the manufacturing process was optimized with a view to minimize surface roughness and maximizing the etching rate by using Design of Experiments. The corresponding pressure drop was measured for flow rates from 0.05 ml min−1 to 0.5 ml min−1.
Published: 2019
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24. Non-Invasive Temperature Measurement for Polyimid-Based Microstructured Devices

Author: Jakob Zimmermann, Jens Bobers, Norbert Kockmann, and Felix Reichmann
Subjects: Materials science, Control theory, Robustness (computer science), Non invasive, Process control, Temperature measurement
Abstract: Besides the common benefits of micro-structured reactors such as enhanced mass and heat transfer caused by a high specific surface and enhanced mixing, they have also drawbacks due to their tiny dimensions. Non-invasive temperature measurement is an important issue for micro process engineering regarding to process control and safety issues. High resolution and robustness are requirements which should be met by the temperature measuring method. Thin film technology combines the possibility to manufacture micro scaled structures with great flexibility in choosing material and geometry of the structures. Layers of aluminum with a thickness in nanometer range are deposited on flexible polyimide foil and structured lithographically to obtain electrical conductor tracks which are used as temperature sensors based on their electrical resistance. The produced temperature sensors were calibrated in the range from 20 to 70 °C and the accuracy of the sensors was checked.
Published: 2019
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25. Cyt-Geist: Current and Future Challenges in Cytometry: Reports of the CYTO 2018 Conference Workshops

Author: Kamila Czechowska, Giacomo Vacca, Cherie Green, Ruth M Barnard, Jaroslav Icha, Michael Nathan Hedrick, Gelo Victoriano Dela Cruz, Nicole E. Paul, Judith Arcidiacono, Andrew Filby, Jakob Zimmermann, Jonni S. Moore, Steven R. Bauer, Ruben Props, Jakub Nedbal, Yongliang Sun, Soren Ulrik Sonder, Christopher Hall, Caryn van Vreden, Cláudia Bispo, Paul K. Wallace, Rachel J. Errington, Jenny Molloy, Joanne Lannigan, Frederik Hammes, Johanna Ivaska, Thomas M. Ashhurst, Frederiek-Maarten Kerckhof, Michael Lee, Hyun-Dong Chang, Christian Kukat, Attila Tárnok, Nao Nitta, Robert S. Hoffman, Gert Van Isterdael, Lina Chakrabarti, John Sharpe, Michael Weber, Raluca Niesner, Christopher Groves, Peter Rubbens, Samson Rogers, Yanli Liu, Dominic Gagnon, Alessandra Vitaliti, Radhika Rayanki, Matthias Schiemann, Lili Wang, Robert Salomon, Grace Chojnowski, Rui Gardner, Bunny Cotleur, Derek H. Jones, John T. Elliott, Betsy Ohlsson-Wilhelm, Stefan Radtke, Maciej Cabanski, Ryan R. Brinkman, Michael Gregory, Henning Ulrich, Jennifer J. Stewart, Sheng Lin-Gibson, Dominic C. Jenner, Heba A. Degheidy, Virginia Litwin, Ziv Portat, Silas J. Leavesley, David Lanham, Susann Müller, Stephen P. Perfetto, Steven Eck, Aja M. Rieger, and Diana L. Bonilla
Subjects: Histology, Drug development, Geist, Immunology, 570 Life sciences, biology, Cell Biology, Computational biology, Biomarker discovery, Biology, 500 Science, Cytometry, Pathology and Forensic Medicine
Published: 2019
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26. Decision letter: IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses

Author: Alexandre Corthay and Jakob Zimmermann
Subjects: Class (set theory), biology, Negative feedback, Immunology, Macrophage, biology.organism_classification, Bacteria
Published: 2019
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27. High‐resolution microbiota flow cytometry reveals dynamic colitis‐associated changes in fecal bacterial composition

Author: Marie Friedrich, Joachim Schumann, René Riedel, Susann Müller, Hyun-Dong Chang, Britta Siegmund, Jakob Zimmermann, Thomas Hübschmann, Rainer Glauben, Andreas Radbruch, Pawel Durek, and Florian Schattenberg
Subjects: 0301 basic medicine, Immunology, IBD, Biology, Technical Comment, Microbiology, Flow cytometry, 03 medical and health sciences, chemistry.chemical_compound, Feces, 0302 clinical medicine, fluids and secretions, Single-cell analysis, RNA, Ribosomal, 16S, medicine, Immunology and Allergy, Animals, Humans, DAPI, Colitis, Single‐cell analysis, Phylogeny, medicine.diagnostic_test, Bacteria, Microbiota, 16S ribosomal RNA, medicine.disease, biology.organism_classification, Flow Cytometry, Inflammatory Bowel Diseases, Staining, Gastrointestinal Microbiome, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, T‐cell transfer colitis
Abstract: Using high-resolution flow cytometry of bacterial shape (forward scatter) and DNA content (DAPI staining), we detected dramatic differences in the fecal microbiota composition during murine colitis that were validated using 16S rDNA sequencing. This innovative method provides a fast and inexpensive tool to interrogate the microbiota on the single-cell level.
Published: 2016

28. Simple transitive $2$-representations of left cell $2$-subcategories of projective functors for star algebras

Author: Jakob Zimmermann
Subjects: Pure mathematics, Transitive relation, Algebra and Number Theory, Functor, 2-representation theory, 010102 general mathematics, 010103 numerical & computational mathematics, Star (graph theory), simple transitive 2-representations, 01 natural sciences, Algebra and Logic, Mathematics::K-Theory and Homology, Simple (abstract algebra), Mathematics::Category Theory, FOS: Mathematics, Cell 2-representations, projective functors, 0101 mathematics, Projective test, Algebra over a field, Representation Theory (math.RT), Mathematics - Representation Theory, Mathematics, Algebra och logik
Abstract: In this paper we study simple transitive $2$-representations of certain $2$-subcategories of the $2$-category of projective functors over a star algebra. We show that in the simplest case, which is associated to the Dynkin type $A_2$, simple transitive $2$-representations are classified by cell $2$-representations. In the general case we conjecture that there exist many simple transitive $2$-representations which are not cell $2$-representations and provide some evidence for our conjecture., 17 pages
Published: 2018

29. Simple transitive $2$-representations of some $2$-categories of projective functors

Author: Jakob Zimmermann
Subjects: Pure mathematics, Transitive relation, Algebra and Number Theory, Functor, 010102 general mathematics, Algebraic geometry, 01 natural sciences, 010305 fluids & plasmas, Quadratic equation, Simple (abstract algebra), Mathematics::Category Theory, 0103 physical sciences, FOS: Mathematics, Geometry and Topology, Tree (set theory), 0101 mathematics, Projective test, Representation Theory (math.RT), Quotient, Mathematics - Representation Theory, Mathematics
Abstract: We show that every simple transitive $2$-representation of the $2$-category of projective functors for a certain quotient of the quadratic dual of the preprojective algebra associated with a tree is equivalent to a cell $2$-representation., 8 pages
Published: 2017

30. 01.07 Control of chronic inflammation by t-bet expressed in th cells

Author: Hyun-Dong Chang, Jakob Zimmermann, and Andreas Radbruch
Subjects: Chemokine, biology, business.industry, T cell, Cell, Inflammation, medicine.disease, Chemokine Expression Profile, Chemokine receptor, medicine.anatomical_structure, Immunology, medicine, biology.protein, Colitis, medicine.symptom, business, Transcription factor
Abstract: Background The transcription factor ‘T-box expressed in T cells’ (T-bet) is highly expressed by Th cells isolated from the inflamed tissue in many chronic inflammatory diseases. Here we have analysed in detail the contribution of T-bet in shaping the inflammation in the T-cell transfer induced colitis model as a prototypic model for T cell mediated chronic, progressive inflammation. Methods To induce colitis Tbx21-deficient Th cells were adoptively transferred into Rag-deficient mice. Intestinal inflammation was characterised by quantitative and qualitative analysis of lamina propria-infiltrating cells, Th cell phenotyping and histology. Results Here we show that the requirement for T-bet expression by Th cells for the manifestation of clinical symptoms of T cell-induced colitis is absolutely dependent on the composition of the intestinal microbiota. When colitis develops, T-bet exerts several non-redundant functions in shaping the inflammation. T-bet expressed by Th cells promotes the survival and positioning of the Th cells in the colon and their repertoire of chemokine and chemokine receptor expression, the recruitment of myeloid cells to the inflamed colon, and the differentiation of macrophages/monocytes. Remarkably, in T cell-induced colitis, T-bet-deficient Th cells differentiate into Th1/17 cells, able to express IFN-γ and IL-17 upon restimulation. Th cell-derived IFN-γ or IL-17, however, are not required to induce colitis. Conclusions We demonstrate that while T-bet shapes the type of the intestinal inflammatory reaction, it is not an essential pre-requisites for T cell-induced colitis. Our data show that the key cytokines IFN-γ and IL-17 play a subordinate role in colitis induction and suggest that the type of inflammation is determined by the chemokine expression profile of the Th cells. In addition, whether Th cells are pathogenic is largely determined by the composition of the intestinal microbiota. Thus, our data shed light on the heterogeneity of inflammatory bowel diseases and their variable response to therapy depending on the microbiota composition and the Th cells involved.
Published: 2017
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31. Authentic IgM Fc Receptor (FcμR)

Author: Kazuhito Honjo, Hyun-Dong Chang, Christopher Mark Skopnik, Luigi F. Bertoli, Hiromi Kubagawa, Pawel Durek, Esther M. Yoo, Jakob Zimmermann, and Andreas Radbruch
Subjects: 0301 basic medicine, Igm antibody, Effector, Fc receptor, Biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, IgM Fc receptor, Cellular distribution, Immunology, biology.protein, Receptor, Function (biology), 030215 immunology
Abstract: Since the bona fide Fc receptor for IgM antibody (FcµR) was identified eight years ago, much progress has been made in defining its biochemical nature, cellular distribution, and effector function. However, there are clearly conflicting results, especially about the cellular distribution and function of murine FcµR. In this short article, we will discuss recent findings from us and other investigators along with our interpretations and comments that may help to resolve the existing puzzles and should open new avenues of investigation.
Published: 2017
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32. Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo

Author: Katrin Lehmann, Mir-Farzin Mashreghi, Georg Petkau, Franziska Zügel, Nikolaus Rajewsky, Markus Bardua, Melanie Weber, Falk Hiepe, Gitta Anne Heinz, Sebastian Herzog, Cam Loan Tran, Sarah Schimmelpfennig, Jakob Zimmermann, Claudia Haftmann, Fritz Melchers, René Riedel, Anja A. Kühl, Francesco Siracusa, Hyun-Dong Chang, Jürgen Wittmann, Andreas Radbruch, Patrick Maschmeyer, Bimba F. Hoyer, Petkau, Georg [0000-0002-6687-2667], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Oligonucleotide therapy, Colon, Immunology, Inflammation, Article, Inflammatory bowel disease, Mice, 03 medical and health sciences, In vivo, microRNA, medicine, Animals, Humans, Immunology and Allergy, Colitis, Cells, Cultured, Oligonucleotide, Chemistry, Effector, Twist-Related Protein 1, Antibody titer, Antagomirs, Nuclear Proteins, Pro-inflammatory Th1 cells, Cell Differentiation, Gamma globulin, Chronic inflammation, Th1 Cells, medicine.disease, miRNA-148a, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, MicroRNAs, 030104 developmental biology, Cancer research, medicine.symptom, T-Box Domain Proteins, Pre-clinical study
Abstract: In T lymphocytes, expression of miR-148a is induced by T-bet and Twist1, and is specific for pro-inflammatory Th1 cells. In these cells, miR-148a inhibits the expression of the pro-apoptotic protein Bim and promotes their survival. Here we use sequence-specific cholesterol-modified oligonucleotides against miR-148a (antagomir-148a) for the selective elimination of pro-inflammatory Th1 cells in vivo. In the murine model of transfer colitis, antagomir-148a treatment reduced the number of pro-inflammatory Th1 cells in the colon of colitic mice by 50% and inhibited miR-148a expression by 71% in the remaining Th1 cells. Expression of Bim protein in colonic Th1 cells was increased. Antagomir-148a-mediated reduction of Th1 cells resulted in a significant amelioration of colitis. The effect of antagomir-148a was selective for chronic inflammation. Antigen-specific memory Th cells that were generated by an acute immune reaction to nitrophenylacetyl-coupled chicken gamma globulin (NP-CGG) were not affected by treatment with antagomir-148a, both during the effector and the memory phase. In addition, antibody titers to NP-CGG were not altered. Thus, antagomir-148a might qualify as an effective drug to selectively deplete pro-inflammatory Th1 cells of chronic inflammation without affecting the protective immunological memory., Highlights • Th1 cells expressing miR-148a mediate colitis in a murine model of IBD. • Antagomir-148a inhibits colitis by selectively depleting Th1 cells from the colon. • Antagomir-148a does not affect the protective immunological memory.
Published: 2017

33. Simple transitive 2-representations of small quotients of Soergel bimodules

Author: Marco Mackaay, Tobias Kildetoft, Jakob Zimmermann, and Volodymyr Mazorchuk
Subjects: Pure mathematics, General Mathematics, Cells, 01 natural sciences, Polynomials, Categories, Mathematics::K-Theory and Homology, Simple (abstract algebra), Mathematics::Category Theory, Mathematics::Quantum Algebra, 0103 physical sciences, FOS: Mathematics, Category Theory (math.CT), 0101 mathematics, Algebra over a field, Representation Theory (math.RT), Mathematics::Representation Theory, Quotient, Mathematics, Transitive relation, Mathematics::Combinatorics, Mathematics::Operator Algebras, Applied Mathematics, 010102 general mathematics, Coxeter group, Mathematics::Rings and Algebras, Mathematics - Category Theory, 010307 mathematical physics, Mathematics - Representation Theory
Abstract: In all finite Coxeter types but $I_2(12)$, $I_2(18)$ and $I_2(30)$, we classify simple transitive $2$-rep\-re\-sen\-ta\-ti\-ons for the quotient of the $2$-category of Soergel bimodules over the coinvariant algebra which is associated to the two-sided cell that is the closest one to the two-sided cell containing the identity element. It turns out that, in most of the cases, simple transitive $2$-representations are exhausted by cell $2$-representations. However, in Coxeter types $I_2(2k)$, where $k\geq 3$, there exist simple transitive $2$-representations which are not equivalent to cell $2$-representations., Revised version to appear in Trans. AMS
Published: 2016

34. T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis

Author: Julia Löffler, Patrick Maschmeyer, Claudia Haftmann, Jakob Zimmermann, Max Löhning, René Riedel, H.-D. Chang, Anja A. Kühl, Katrin Lehmann, Joachim R. Grün, Michael Weber, Mir-Farzin Mashreghi, Matthias Mack, Andreas Radbruch, and Kerstin Westendorf
Subjects: 0301 basic medicine, Chemokine, Cellular differentiation, Immunology, Gene Expression, chemical and pharmacologic phenomena, Inflammation, Biology, Monocytes, 03 medical and health sciences, Chemokine receptor, Interferon-gamma, Mice, medicine, Immunology and Allergy, Animals, Interferon gamma, Lymphocyte Count, Colitis, Mice, Knockout, Macrophages, Interleukin-17, hemic and immune systems, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Th1 Cells, biology.organism_classification, medicine.disease, Disease Models, Animal, 030104 developmental biology, biology.protein, Th17 Cells, Interleukin 17, Helicobacter hepaticus, medicine.symptom, T-Box Domain Proteins, medicine.drug
Abstract: The transcription factor T-bet is highly expressed by Th cells isolated from the inflamed intestine of Crohn's disease patients, and has been regarded a critical driver of murine T cell-induced colitis. However, we show here that T-bet expression by Th cells is not required for the manifestation of T-cell-induced colitis in the presence of segmented filamentous bacteria and Helicobacter hepaticus. T-bet expression by Th cells controls their survival and localization, their repertoire of chemokine and chemokine receptor expression, the accumulation of monocytes and macrophages in the inflamed colon, and their differentiation to the M1 type, i.e., type 1 inflammation. Nevertheless, T-bet-deficient Th cells efficiently induce colitis, as reflected by weight loss, diarrhea, and colon histopathology. T-bet-deficient Th cells differentiate into Th1/17 cells, able to express IFN-γ and IL-17A upon restimulation. While neutralization of IL-17A exacerbated colitis induced by wild-type or T-bet-deficient Th cells, neutralization of IFN-γ completely abolished colitis.
Published: 2015

35. MiR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim

Author: Gitta Anne Heinz, Nikolaus Rajewsky, Markus Bardua, Hans-Martin Jäck, Marina Backhaus, Anna-Barbara Stittrich, Wei-Wei Chen, Max Löhning, Claudia Haftmann, Jakob Zimmermann, Mareen Matz, Joachim Sieper, Christian Neumann, Joachim R. Grün, Uta Lauer, Kristyna Hradilkova, Alexander Scheffold, Julia Siede, René Riedel, Jürgen Wittmann, Hyun-Dong Chang, Andreas Radbruch, Esther E. Weinberger, Mir-Farzin Mashreghi, Ute Hoffmann, Martina Porstner, Katrin Lehmann, Thomas Häupl, Ria Baumgrass, David Zimmel, Kerstin Westendorf, and Zhuo Fang
Subjects: Apoptosis, Arthritis, Rheumatoid, Th1, Twist transcription factor, Mice, 0302 clinical medicine, RNA interference, hemic and lymphatic diseases, Immunology and Allergy, RNA, Small Interfering, Cells, Cultured, Regulation of gene expression, Mice, Knockout, 0303 health sciences, Gene knockdown, Mice, Inbred BALB C, Bcl-2-Like Protein 11, Nuclear Proteins, hemic and immune systems, 3. Good health, Cell biology, miR-148a, Bim, Mir-148a, T-bet, Twist1, RNA Interference, medicine.symptom, Technology Platforms, biological phenomena, cell phenomena, and immunity, Molecular Immunology, Cell Survival, Immunology, Inflammation, chemical and pharmacologic phenomena, Biology, 03 medical and health sciences, Downregulation and upregulation, Proto-Oncogene Proteins, microRNA, medicine, Animals, Humans, Transcription factor, 030304 developmental biology, Twist-Related Protein 1, Membrane Proteins, Th1 Cells, Molecular biology, Mice, Inbred C57BL, MicroRNAs, Gene Expression Regulation, Cardiovascular and Metabolic Diseases, Apoptosis Regulatory Proteins, T-Box Domain Proteins, 030215 immunology
Abstract: Repeatedly activated T helper 1 (Th1) cells present during chronic inflammation can efficiently adapt to the inflammatory milieu, for example, by expressing the transcription factor Twist1, which limits the immunopathology caused by Th1 cells. Here, we show that in repeatedly activated murine Th1 cells, Twist1 and T-bet induce expression of microRNA-148a (miR-148a). miR-148a regulates expression of the proapoptotic gene Bim, resulting in a decreased Bim/Bcl2 ratio. Inhibition of miR-148a by antagomirs in repeatedly activated Th1 cells increases the expression of Bim, leading to enhanced apoptosis. Knockdown of Bim expression by siRNA in miR-148a antagomir-treated cells restores viability of the Th1 cells, demonstrating that miR-148a controls survival by regulating Bim expression. Thus, Twist1 and T-bet not only control the differentiation and function of Th1 cells, but also their persistence in chronic inflammation.
Published: 2015

36. Guidelines for the use of flow cytometry and cell sorting in immunological studies

Author: Guadalupe Herrera, Jens Geginat, Daryl Grummitt, Vincenzo Barnaba, Joanne Lannigan, Beate Rückert, Elisabetta Traggiai, Christian Münz, Susanne Melzer, Ari Waisman, Pratip K. Chattopadhyay, Jonas Hahn, T. Vincent Shankey, S Schmid, Julia Tornack, David W. Hedley, Paolo Dellabona, Jürgen Wienands, Ana Cumano, Ester B. M. Remmerswaal, Christopher A. Hunter, Van Duc Dang, Anis Larbi, Timothy P. Bushnell, Mor Gross, Wenjun Ouyang, Vera S. Donnenberg, Lilly Lopez, Holden T. Maecker, Jenny Mjösberg, Christina Stehle, Yanling Liu, Alan M. Stall, Anja E. Hauser, Yousuke Takahama, Mark C. Dessing, Gergely Toldi, Klaus Warnatz, Raghav Palankar, Sussan Nourshargh, Enrico Lugli, Bimba F. Hoyer, Pleun Hombrink, Bartek Rajwa, Sarah Warth, Isabel Panse, Rachael C. Walker, Silvia Piconese, Andrew Filby, Pärt Peterson, Kilian Schober, Silvia Della Bella, Leonie Wegener, Merle Stein, Anne Cooke, Alessandro Moretta, Deborah Kienhöfer, Andrea Cossarizza, Hyun-Dong Chang, Konrad von Volkmann, Jessica P. Houston, Mübeccel Akdis, Andreas Grützkau, Tristan Holland, Jakob Zimmermann, Jonni S. Moore, Dirk Mielenz, Iain B. McInnes, Bo Huang, Paulo Vieira, Thomas Kroneis, Tobit Steinmetz, Kerstin Juelke, Sharon Sanderson, James V. Watson, Srijit Khan, Sally A. Quataert, Winfried F. Pickl, Annika Wiedemann, Sara De Biasi, Andreas Radbruch, James B. Wing, Susann Müller, Ton N. Schumacher, Katy Rezvani, Gloria Martrus, Alexander Scheffold, Toralf Kaiser, Carlo Pucillo, Lara Gibellini, Anna Rubartelli, Qingyu Cheng, Luca Battistini, David Mirrer, David W. Galbraith, Giovanna Borsellino, Ryan R. Brinkman, Tim R. Mosmann, Laura G. Rico, Anita Dreher, Désirée Kunkel, Francesco Annunziato, Pia Kvistborg, Andrea Gori, Chiara Romagnani, Anat Shemer, Toshinori Nakayama, Francisco Sala-de-Oyanguren, Attila Tárnok, Alfonso Blanco, Anna Iannone, Giuseppe Matarese, Thomas Dörner, Virginia Litwin, Michael Lohoff, Petra Bacher, Jordi Petriz, Lorenzo Moretta, Götz R. A. Ehrhardt, Qianjun Zhang, Andrea Cavani, Barry Moran, Christian Maueröder, Immanuel Andrä, Dirk H. Busch, Joe Trotter, Timothy R D J Radstake, Stipan Jonjić, Fritz Melchers, Hans-Martin Jäck, Beatriz Jávega, Gerald Willimsky, Martin Büscher, Henrik E. Mei, Christine S. Falk, Zhigang Tian, Martin Herrmann, Alice Yue, Steffen Jung, Bart Everts, Frank A. Schildberg, John Bellamy Foster, Giovanna Lombardi, Milena Nasi, John P. Nolan, Todd A. Fehniger, Francesco Dieli, Steffen Schmitt, Andreas Dolf, A. Graham Pockley, Claudia Berek, Josef Spidlen, Megan K. Levings, Werner Müller, Baerbel Keller, René A. W. van Lier, Daisy Philips, Susanne Ziegler, Christian Kurts, Malgorzata J. Podolska, Jürgen Ruland, David Voehringer, Kenneth M. Murphy, Marlous van der Braber, Maria Dolores García-Godoy, Sabine Baumgart, Yi Zhao, Antonio Cosma, Falk Hiepe, Charlotte Esser, Pablo Engel, Marcello Veldhoen, Irmgard Förster, Amy E. Lovett-Racke, Günnur Deniz, Burkhard Ludewig, Esther Schimisky, Cristiano Scottà, Marcello Pinti, Jonathan Rebhahn, Regina Stark, Mario Clerici, Liping Yu, Shimon Sakaguchi, Derek Davies, Anna Katharina Simon, Lorenzo Cosmi, Gabriele Multhoff, Kamran Ghoreschi, Quirin Hammer, Henning Ulrich, J. Paul Robinson, Yvonne Samstag, Olivier Lantz, Hannes Stockinger, Xuetao Cao, Simon Fillatreau, David L. Haviland, Natalio Garbi, C. Neudörfl, Kingston H. G. Mills, Salvador Vento-Asturias, Christian Peth, Philip E. Boulais, Diether J. Recktenwald, Burkhard Becher, Tomas Kalina, Michael D. Leipold, Christoph Goettlinger, Gemma A. Foulds, Jane L. Grogan, Axel R. Schulz, James P. Di Santo, Matthias Schiemann, Michael D. Ward, Britta Engelhardt, Birgit Sawitzki, Annette Oxenius, Carl S. Goodyear, Salomé LeibundGut-Landmann, Wolfgang Beisker, Sue Chow, Carsten Watzl, Marie Follo, Erik Lubberts, Peter Wurst, Thomas Schüler, Andreas Diefenbach, Wolfgang Bauer, Hans-Dieter Volk, Luis E. Muñoz, Elmar Endl, Genny Del Zotto, José-Enrique O'Connor, Mairi McGrath, Paul S. Frenette, Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Cell Biology, Klinik für Dermatologie, Venerologie und Allergologie, Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Neuroimmunology Unit, Santa Lucia Foundation (IRCCS), Inorganic Chemistry II, Universität Bayreuth, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, Institut der Leibniz-Gemeinschaft, Berlin, Fondazione Santa Lucia (IRCCS), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Immunology, Chinese Academy of Medical Sciences, Fondazione Don Carlo Gnocchi, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Département d'Immunologie - Department of Immunology, Institut Pasteur [Paris], Charité Hospital, Humboldt-Universität zu Berlin, Universitat de Barcelona (UB), Rheumatologie, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Department of Histology and Embryology, University of Rijeka, Weizmann Institute of Science [Rehovot, Israël], Régulation des Infections Rétrovirales, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Institute of Virology [Zürich], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, Centre for Transplantation, King's College London (MRC), Guy's Hospital [London], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Institute, Heinrich Pette Institute [Hamburg], Institute of Translational Medicine, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Experimental Immunology, Helmholtz Centre for Infection Research (HZI), Viral Immunobiology, Universität Zürich [Zürich] = University of Zurich (UZH)-Institute of Experimental Immunology [Zurich], Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Department of Mathematics and Statistics, American University, William Harvey Research Institute, Barts and the London Medical School, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Osaka University [Osaka], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Institute for Cognitive Science, University of Osnabrueck, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Universität Leipzig [Leipzig], Institute of Immunology, School of Life Sciences-University of Science & Technology of China [Suzhou], Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Immunology, Processus de Transfert et d'Echanges dans l'Environnement - EA 3819 (PROTEE), Université de Toulon (UTLN), Heinrich-Pette-Institut, Leibniz Institute for Experimental Virology, Enrico Lugli and Pratip K. Chattopadhyay were supported by grants from the Fondazione Cariplo (Grant Ricerca Biomedica 2012/0683), the Italian Ministry of Health (Bando Giovani Ricercatori GR-2011-02347324) and the European Union Marie Curie Career Integration Grant 322093 (all to E.L.). E.L. and P.K.C. are International Society for the Advancement of Cytometry (ISAC) Marylou Ingram scholars. Alice Yue and Ryan R. Brinkman were funded by Genome BC and NSERC. Klaus Warnatz received funding from the German Federal Ministry of Education and Research (BMBF 01EO1303) and the Deutsche Forschungsgemeinschaft (DECIDE, DFG WA 1597/4-1 and the TRR130). The Jung laboratory is supported by funds of the ERC and ISF. Henrik Mei is a 2017-2021 ISAC scholar. Antonio Cosma is supported by the French government program: 'Investissement d'avenir: Equipements d'Excellence' (EQUIPEX)-2010 FlowCyTech, Grant number: ANR-10-EQPX-02-01. Henrik Mei is supported by the Deutsche Forschungsgemeinschaft (DFG, grants Me3644/5-1 and TRR130/TP24)., Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Institut Pasteur [Paris] (IP), Humboldt University Of Berlin, Universität Bonn = University of Bonn, Università degli studi di Genova = University of Genoa (UniGe), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Universität Leipzig, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Obstetrics & Gynecology, Rheumatology, Pediatrics, Landsteiner Laboratory, Other departments, AII - Inflammatory diseases, Università di Modena e Reggio Emilia, DENOTHE Center-University of Florence, Santa Lucia Foundation ( IRCCS ), International Occultation Timing Association European Section ( IOTA ES ), Fondazione Santa Lucia ( IRCCS ), BC Cancer Agency ( BCCRC ) -British Columbia Cancer Agency Research Centre, Fondazione don Carlo Gnocchi, Fondazione IRCCS, Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'Immunologie, Humboldt Universität zu Berlin, Universitat de Barcelona ( UB ), Charité, Weizmann Institute of Science, Université de Bonn, Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Singapore Immunology Network ( SIgN ), Agency for Science Technology and Research, College of Food Science and Technology, Centre for Transplantation, King's College London ( MRC ), Erasmus MC University Medical Center, Helmholtz Centre for Environmental Research ( UFZ ), Helmholtz Centre for Infection Research ( HZI ), University of Zürich [Zürich] ( UZH ) -Institute of Experimental Immunology [Zurich], Ludwig-Maximilians-Universität München, Johannes Gutenberg - Universität Mainz ( JGU ), Medical University of Vienna, Lymphopoïèse, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Johannes Gutenberg - University of Mainz ( JGU ), Processus de Transfert et d'Echanges dans l'Environnement - EA 3819 ( PROTEE ), Université de Toulon ( UTLN ), Universita degli studi di Genova, Cossarizza, Andrea, Chang, Hyun-Dong, Radbruch, Andrea, Akdis, Mübeccel, Andrä, Immanuel, Annunziato, Francesco, Bacher, Petra, Barnaba, Vincenzo, Battistini, Luca, Bauer, Wolfgang M., Baumgart, Sabine, Becher, Burkhard, Beisker, Wolfgang, Berek, Claudia, Blanco, Alfonso, Borsellino, Giovanna, Boulais, Philip E., Brinkman, Ryan R., Büscher, Martin, Busch, Dirk H., Bushnell, Timothy P., Cao, Xuetao, Cavani, Andrea, Chattopadhyay, Pratip K., Cheng, Qingyu, Chow, Sue, Clerici, Mario, Cooke, Anne, Cosma, Antonio, Cosmi, Lorenzo, Cumano, Ana, Dang, Van Duc, Davies, Derek, De Biasi, Sara, Del Zotto, Genny, Della Bella, Silvia, Dellabona, Paolo, Deniz, Günnur, Dessing, Mark, Diefenbach, Andrea, Di Santo, Jame, Dieli, Francesco, Dolf, Andrea, Donnenberg, Vera S., Dörner, Thoma, Ehrhardt, Götz R. A., Endl, Elmar, Engel, Pablo, Engelhardt, Britta, Esser, Charlotte, Everts, Bart, Dreher, Anita, Falk, Christine S., Fehniger, Todd A., Filby, Andrew, Fillatreau, Simon, Follo, Marie, Förster, Irmgard, Foster, John, Foulds, Gemma A., Frenette, Paul S., Galbraith, David, Garbi, Natalio, García-Godoy, Maria Dolore, Geginat, Jen, Ghoreschi, Kamran, Gibellini, Lara, Goettlinger, Christoph, Goodyear, Carl S., Gori, Andrea, Grogan, Jane, Gross, Mor, Grützkau, Andrea, Grummitt, Daryl, Hahn, Jona, Hammer, Quirin, Hauser, Anja E., Haviland, David L., Hedley, David, Herrera, Guadalupe, Herrmann, Martin, Hiepe, Falk, Holland, Tristan, Hombrink, Pleun, Houston, Jessica P., Hoyer, Bimba F., Huang, Bo, Hunter, Christopher A., Iannone, Anna, Jäck, Hans-Martin, Jávega, Beatriz, Jonjic, Stipan, Juelke, Kerstin, Jung, Steffen, Kaiser, Toralf, Kalina, Toma, Keller, Baerbel, Khan, Srijit, Kienhöfer, Deborah, Kroneis, Thoma, Kunkel, Désirée, Kurts, Christian, Kvistborg, Pia, Lannigan, Joanne, Lantz, Olivier, Larbi, Ani, LeibundGut-Landmann, Salome, Leipold, Michael D., Levings, Megan K., Litwin, Virginia, Liu, Yanling, Lohoff, Michael, Lombardi, Giovanna, Lopez, Lilly, Lovett-Racke, Amy, Lubberts, Erik, Ludewig, Burkhard, Lugli, Enrico, Maecker, Holden T., Martrus, Glòria, Matarese, Giuseppe, Maueröder, Christian, Mcgrath, Mairi, Mcinnes, Iain, Mei, Henrik E., Melchers, Fritz, Melzer, Susanne, Mielenz, Dirk, Mills, Kingston, Mirrer, David, Mjösberg, Jenny, Moore, Jonni, Moran, Barry, Moretta, Alessandro, Moretta, Lorenzo, Mosmann, Tim R., Müller, Susann, Müller, Werner, Münz, Christian, Multhoff, Gabriele, Munoz, Luis Enrique, Murphy, Kenneth M., Nakayama, Toshinori, Nasi, Milena, Neudörfl, Christine, Nolan, John, Nourshargh, Sussan, O'Connor, José-Enrique, Ouyang, Wenjun, Oxenius, Annette, Palankar, Raghav, Panse, Isabel, Peterson, Pärt, Peth, Christian, Petriz, Jordi, Philips, Daisy, Pickl, Winfried, Piconese, Silvia, Pinti, Marcello, Pockley, A. Graham, Podolska, Malgorzata Justyna, Pucillo, Carlo, Quataert, Sally A., Radstake, Timothy R. D. J., Rajwa, Bartek, Rebhahn, Jonathan A., Recktenwald, Diether, Remmerswaal, Ester B. M., Rezvani, Katy, Rico, Laura G., Robinson, J. Paul, Romagnani, Chiara, Rubartelli, Anna, Ruckert, Beate, Ruland, Jürgen, Sakaguchi, Shimon, Sala-de-Oyanguren, Francisco, Samstag, Yvonne, Sanderson, Sharon, Sawitzki, Birgit, Scheffold, Alexander, Schiemann, Matthia, Schildberg, Frank, Schimisky, Esther, Schmid, Stephan A., Schmitt, Steffen, Schober, Kilian, Schüler, Thoma, Schulz, Axel Ronald, Schumacher, Ton, Scotta, Cristiano, Shankey, T. Vincent, Shemer, Anat, Simon, Anna-Katharina, Spidlen, Josef, Stall, Alan M., Stark, Regina, Stehle, Christina, Stein, Merle, Steinmetz, Tobit, Stockinger, Hanne, Takahama, Yousuke, Tarnok, Attila, Tian, Zhigang, Toldi, Gergely, Tornack, Julia, Traggiai, Elisabetta, Trotter, Joe, Ulrich, Henning, van der Braber, Marlou, van Lier, René A. W., Veldhoen, Marcello, Vento-Asturias, Salvador, Vieira, Paulo, Voehringer, David, Volk, Hans-Dieter, von Volkmann, Konrad, Waisman, Ari, Walker, Rachael, Ward, Michael D., Warnatz, Klau, Warth, Sarah, Watson, James V., Watzl, Carsten, Wegener, Leonie, Wiedemann, Annika, Wienands, Jürgen, Willimsky, Gerald, Wing, Jame, Wurst, Peter, Yu, Liping, Yue, Alice, Zhang, Qianjun, Zhao, Yi, Ziegler, Susanne, Zimmermann, Jakob, Cossarizza, A., Chang, H., Radbruch, A., Akdis, M., Andrã¤, I., Annunziato, F., Bacher, P., Barnaba, V., Battistini, L., Bauer, W., Baumgart, S., Becher, B., Beisker, W., Berek, C., Blanco, A., Borsellino, G., Boulais, P., Brinkman, R., Bã¼scher, M., Busch, D., Bushnell, T., Cao, X., Cavani, A., Chattopadhyay, P., Cheng, Q., Chow, S., Clerici, M., Cooke, A., Cosma, A., Cosmi, L., Cumano, A., Dang, V., Davies, D., De Biasi, S., Del Zotto, G., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Diefenbach, A., Di Santo, J., Dieli, F., Dolf, A., Donnenberg, V., Dã¶rner, T., Ehrhardt, G., Endl, E., Engel, P., Engelhardt, B., Esser, C., Everts, B., Dreher, A., Falk, C., Fehniger, T., Filby, A., Fillatreau, S., Follo, M., Fã¶rster, I., Foster, J., Foulds, G., Frenette, P., Galbraith, D., Garbi, N., GarcÃa-Godoy, M., Geginat, J., Ghoreschi, K., Gibellini, L., Goettlinger, C., Goodyear, C., Gori, A., Grogan, J., Gross, M., Grã¼tzkau, A., Grummitt, D., Hahn, J., Hammer, Q., Hauser, A., Haviland, D., Hedley, D., Herrera, G., Herrmann, M., Hiepe, F., Holland, T., Hombrink, P., Houston, J., Hoyer, B., Huang, B., Hunter, C., Iannone, A., Jã¤ck, H., Jã¡vega, B., Jonjic, S., Juelke, K., Jung, S., Kaiser, T., Kalina, T., Keller, B., Khan, S., Kienhã¶fer, D., Kroneis, T., Kunkel, D., Kurts, C., Kvistborg, P., Lannigan, J., Lantz, O., Larbi, A., LeibundGut-Landmann, S., Leipold, M., Levings, M., Litwin, V., Liu, Y., Lohoff, M., Lombardi, G., Lopez, L., Lovett-Racke, A., Lubberts, E., Ludewig, B., Lugli, E., Maecker, H., Martrus, G., Matarese, G., Mauerã¶der, C., Mcgrath, M., Mcinnes, I., Mei, H., Melchers, F., Melzer, S., Mielenz, D., Mills, K., Mirrer, D., Mjã¶sberg, J., Moore, J., Moran, B., Moretta, A., Moretta, L., Mosmann, T., Mã¼ller, S., Mã¼ller, W., Mã¼nz, C., Multhoff, G., Munoz, L., Murphy, K., Nakayama, T., Nasi, M., Neudã¶rfl, C., Nolan, J., Nourshargh, S., O'Connor, J., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Peterson, P., Peth, C., Petriz, J., Philips, D., Pickl, W., Piconese, S., Pinti, M., Pockley, A., Podolska, M., Pucillo, C., Quataert, S., Radstake, T., Rajwa, B., Rebhahn, J., Recktenwald, D., Remmerswaal, E., Rezvani, K., Rico, L., Robinson, J., Romagnani, C., Rubartelli, A., Ruckert, B., Ruland, J., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sawitzki, B., Scheffold, A., Schiemann, M., Schildberg, F., Schimisky, E., Schmid, S., Schmitt, S., Schober, K., Schã¼ler, T., Schulz, A., Schumacher, T., Scotta, C., Shankey, T., Shemer, A., Simon, A., Spidlen, J., Stall, A., Stark, R., Stehle, C., Stein, M., Steinmetz, T., Stockinger, H., Takahama, Y., Tarnok, A., Tian, Z., Toldi, G., Tornack, J., Traggiai, E., Trotter, J., Ulrich, H., van der Braber, M., van Lier, R., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H., von Volkmann, K., Waisman, A., Walker, R., Ward, M., Warnatz, K., Warth, S., Watson, J., Watzl, C., Wegener, L., Wiedemann, A., Wienands, J., Willimsky, G., Wing, J., Wurst, P., Liping, Y., Yue, A., Zhang, Q., Zhao, Y., Ziegler, S., and Zimmermann, J.
Subjects: 0301 basic medicine, T-Lymphocytes, Cell Separation, T cell precursors, 0302 clinical medicine, Immunophenotyping, Human lymphopoiesis, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Non-U.S. Gov't, Immunologic Technique, medicine.diagnostic_test, Research Support, Non-U.S. Gov't, virus diseases, hemic and immune systems, False Positive Reaction, Cell sorting, Flow Cytometry, natural killer and innate lymphoid cells differentiation, 3. Good health, Research Design, [SDV.IMM]Life Sciences [q-bio]/Immunology, Human, Quality Control, medicine.drug_class, Immunology, Animals, Cell Proliferation, DNA, False Positive Reactions, Humans, RNA, Software, Guidelines as Topic, Immunologic Techniques, chemical and pharmacologic phenomena, Computational biology, Biology, Monoclonal antibody, Research Support, Article, Flow cytometry, N.I.H, 03 medical and health sciences, Immune system, Research Support, N.I.H., Extramural, medicine, early lymphoid progenitors, Journal Article, Mass cytometry, IMUNOLOGIA, Animal, Extramural, B cell ontogeny, 030104 developmental biology, T-Lymphocyte, Cytometry, 030215 immunology
Abstract: The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.
Published: 2017
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37. A Ca(2+) concentration of 1.5 mM, as present in IMDM but not in RPMI, is critical for maximal response of Th cells to PMA/ionomycin

Author: Hyun-Dong Chang, Jakob Zimmermann, and Andreas Radbruch
Subjects: Immunology, Cell Culture Techniques, chemistry.chemical_element, Biology, Calcium, Lymphocyte Activation, Technical Comment, Flow cytometry, Cellular activation, chemistry.chemical_compound, Mice, medicine, Immunology and Allergy, Animals, Humans, Cytokine genes, Mice, Knockout, medicine.diagnostic_test, Ionomycin, T-Lymphocytes, Helper-Inducer, Colitis, Molecular biology, CD4+ T cells, Culture Media, Calcineurin, Mice, Inbred C57BL, PMA/ionomycin, chemistry, Cell culture, Lymphocyte activation, Cytokines
Abstract: Restimulation of memory–effector T helper lymphocytes with PMA/ionomycin is an established technique to determine their imprinting for the expression of cytokine genes, that is their functional potential. Here, we show that for the maximal reexpression of cytokine genes, the Ca2+ concentration of the medium has to be greater than 1.5 mM. For RPMI (Roswell Park Memorial Institute 1640), the most commonly used medium, the Ca2+ concentration has to be increased from the regular 0.42 to 1.5 mM.
Published: 2014

38. EXTREME REPRESENTATIONS OF SEMIRINGS.

Author: Chih-Whi Chen, Dubsky, Brendan Frisk, Jonsson, Helena, Mazorchuk, Volodymyr, Westin, Elin Persson, Xiaoting Zhang, and Jakob Zimmermann
Abstract: This is a write-up of the discussions during the meetings of the study group on representation theory of semirings which was organized at the Department of Mathematics, Uppsala University, during the academic year 2017-2018. The main emphasis is on classification of various classes of "irreducible" representations for various concrete semirings. [ABSTRACT FROM AUTHOR]
Published: 2018

39. A7.19 Systemic inhibition of MIR-148A by antagomirs reduces CD4+T helper cell numbers and alleviates inflammation in a preclinical model of transfer colitis

Author: Cam Loan Tran, B. Rausch, Andreas Radbruch, M. F. Mashreghi, Patrick Maschmeyer, Jakob Zimmermann, René Riedel, Claudia Haftmann, Sebastian Herzog, and H.-D. Chang
Subjects: medicine.diagnostic_test, business.industry, Immunology, Cell, Stimulation, Inflammation, T helper cell, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Flow cytometry, Proinflammatory cytokine, medicine.anatomical_structure, Rheumatology, microRNA, medicine, Cancer research, Immunology and Allergy, Colitis, medicine.symptom, business
Abstract: Background and objectives T helper type 1 (Th1) cells are involved in rheumatic diseases such as Crohn´s disease or rheumatoid arthritis and have a history of chronic autoantigenic stimulation. We have shown that Th1 cells adapt to chronic inflammation by upregulating the expression of the microRNA (miR)-148a. MiR-148a promotes the survival of chronically activated Th1 cells by regulating the expression of the proapoptotic protein Bim. Thus, we tested the suitability of miR-148a as a therapeutic target for the selective elimination of proinflammatory Th1 cells in a preclinical model of colitis. Methods Chronically activated Th1 cells were transferred into Rag1-deficient mice to induce colitis. Then, mice were intravenously injected with antagomirs that specifically target the microRNA-148a (antagomir-148a) or with control antagomirs (antagomir-scr). For assessing the function of T cell-intrinsic expression of miR-148a in colitis, we transduced Th1 cells with inducible microRNA sponges prior to transfer into Rag1-deficient mice. Colitic inflammation was determined by the weight-to-length ratios of colons. Colonic Th cells were sorted by FACS to measure miR-148a expression by qRT-PCR. The expression of Bim and Bcl-2 as well as numbers of viable Th1 cells, were determined by flow cytometry. Results Systemic inhibition of miR-148a by antagomirs alleviated colitis in mice as measured by reduced weight-to-length ratios of their colons. The numbers of viable Th1 cells were reduced up to 50% in mice that were treated with antagomir-148a when compared to mice that were injected with antagomir-scr. Antagomir-148a injections were efficient and resulted in a 30% reduction of miR-148a in colonic Th1 cells. The expression of the proapoptotic protein Bim was increased up to 30% in Th cells from antagomir-148a treated mice, while the anti-apoptotic protein Bcl-2 was unchanged. Th cell specific inhibition of miR-148a by miR-sponges during colitis led to a 30% reduction of Th cells in the colons of colitic mice and reduced the weight-to-length ratio. Conclusions We suggest that miR-148a controls the survival of proinflammatory Th1 cells in chronic inflammation by inhibiting Bim expression in a Th cell intrinsic fashion. Thus, miR-148a might represent a suitable target for the selective depletion of proinflammatory Th1 cells in chronic inflammation.
Published: 2016
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40. AB0038 Modulation of the Survival of Proinflammatory TH1 Lymphocytes by Stable Expression of MIR-148A Sponges in a Murine Model of Transfer Colitis

Author: M. F. Mashreghi, Patrick Maschmeyer, Jakob Zimmermann, Andreas Radbruch, René Riedel, B. Rausch, H.-D. Chang, Sebastian Herzog, Claudia Haftmann, and Cam Loan Tran
Subjects: Transgene, Immunology, Cell, Inflammation, Biology, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Proinflammatory cytokine, medicine.anatomical_structure, Rheumatology, Downregulation and upregulation, Gene expression, Cancer research, medicine, Immunology and Allergy, media_common.cataloged_instance, medicine.symptom, European union, Colitis, media_common
Abstract: Background Proinflammatory T helper (Th) cells are critically involved in the initiation and perpetuation of chronic inflammatory diseases (CID). In these diseases, proinflammatory Th cells persist in inflamed tissues and are refractory to current immunosuppressive therapies. The molecular factors regulating the survival of proinflammatory Th cells are not fully understood. Recently, we have shown that proinflammatory Th1 cells adapt to chronic inflammation by upregulating the expression of the microRNA (miRNA, miR)-148a 1 . MiR-148a promotes the survival of proinflammatory Th1 cells by regulating the expression of the pro-apoptotic protein Bim. Memory Th cells isolated from inflamed synovia of patients with rheumatoid arthritis induce the expression of miR-148a, presumably enhancing their survival. Therefore we hypothesize, that miR-148a could represent a therapeutic target for the selective elimination of proinflammatory Th1 cells in CID. Objectives To test the suitability of miR-148a as a therapeutic target in a preclinical murine model of transfer colitis. Methods We have generated a retroviral based inducible miR-148a inhibitor, containing complementary binding sites for miR-148a, termed “miR-148a sponge”. We transduced transgenic Th cells with the miR-148a sponge or a scrambled (scr) control sponge. Induction of sponge expression was initiated by tamoxifen treatment. Expression of miRNA sponges was detected by GFP reporter gene expression and the functionality of miR148a inhibition was determined by real-time PCR for the miR-148a target Bim. MiR-148a sponge-transduced CD4 + Th1 cells were FACS-sorted and transferred into Rag1 -/- mice. After manifestation of colitis, mice were sacrificed and T cells were re-isolated from the spleens and colons for determining their phenotype and number by FACS analysis. Results Expression of miR-148a sponges resulted in a 2 fold increase of Bim expression in activated Th1 cells in vitro . In addition, we found reduced numbers of miR-148a-sponge expressing Th cells as compared to scr-sponge expressing Th cells in the spleens and colons of colitic mice. Finally, miR-148a sponge-expressing Th cells from spleens and colons of colitic mice showed higher levels of Bim expression per cell than scr-sponge expressing cells. Conclusions Our data suggest that miR-148a controls the survival of pro-inflammatory Th1 cells in chronic inflammation by inhibiting Bim expression. Thus, therapeutic targeting of miR-148a probably is suitable for the selective depletion of proinflammatory Th1 cells in chronic inflammation. References Haftmann, C. et al. miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim. European journal of immunology, doi:10.1002/eji.201444633 (2014). Acknowledgements Patrick Maschmeyer is supported by EUTRAIN, a FP7 Marie Curie Initial Training Network for Early Stage Researchers funded by the European Union. Disclosure of Interest None declared
Published: 2015
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41. Breast Milk Modulates Transgenerational Immune Inheritance

Author: Jakob Zimmermann and Andrew J. Macpherson
Subjects: Immunoglobulin A, Cell, Inflammation, Biology, Breast milk, T-Lymphocytes, Regulatory, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Transgenerational epigenetics, medicine, Humans, Pathogen, 030304 developmental biology, 0303 health sciences, Milk, Human, Inheritance (genetic algorithm), food and beverages, Nuclear Receptor Subfamily 1, Group F, Member 3, Gastrointestinal Microbiome, medicine.anatomical_structure, Immunology, biology.protein, Th17 Cells, Female, medicine.symptom, 030217 neurology & neurosurgery
Abstract: At the species level, immunity depends on the selection and transmission of protective components of the immune system. A microbe-induced population of RORγ-expressing T regulatory cells (Tregs) is essential in controlling gut inflammation. We uncovered a non-genetic, non-epigenetic, non-microbial, mode of transmission of their homeostatic setpoint. RORγ(+) Treg proportions varied between inbred mouse strains, a trait transmitted by the mother during a tight age-window after birth but stable for life, resistant to many microbial or cellular perturbations, then further transferred by females for multiple generations. RORγ(+) Treg proportions negatively correlated with IgA production and coating of gut commensals, traits also subject to maternal transmission, in an immunoglobulin- and RORγ(+) Treg-dependent manner. We propose a model based on a double-negative feedback loop, vertically transmitted via the entero-mammary axis. This immunologic mode of multi-generational transmission may provide adaptability and modulate the genetic tuning of gut immune responses and inflammatory disease susceptibility.
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