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Start Over Author "Yuval Itan" Publisher american association for the advancement of science (aaas)
3 results on '"Yuval Itan"'

1. Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β

Author

Marco Ritelli, Harry C. Dietz, Danielle T. Avery, Bertrand Boisson, Soraya Boucherit, Lucie Grodecká, Stuart G. Tangye, Romain Lévy, Kathryn Payne, Tomáš Freiberger, Sophie Cypowyj, Juan Li, Valérie Cormier-Daire, Nicoletta Zoppi, Laurent Abel, Geetha Rao, Vivien Béziat, Andrea Guennoun, Benedetta Bigio, Maya Chrabieh, Salim Bougarn, Marina Colombi, Lei Shang, Emilie Corvilain, Yuval Itan, Anne Puel, Franck Rapaport, Nico Marr, Fransiska Malfait, Delfien Syx, Mélanie Migaud, Tanwir Habib, Sabri Boughorbel, Jean-Laurent Casanova, and Cindy S. Ma

Subjects
Male, 0301 basic medicine, Connective Tissue Disorder, MAPK8, Immunology, Mucocutaneous zone, Connective tissue, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, medicine, Humans, Mitogen-Activated Protein Kinase 8, Chronic mucocutaneous candidiasis, Connective Tissue Diseases, Alleles, Cells, Cultured, business.industry, Candidiasis, Chronic Mucocutaneous, Interleukin-17, General Medicine, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, Signal transduction, Haploinsufficiency, business
Abstract

Genetic etiologies of chronic mucocutaneous candidiasis (CMC) disrupt human IL-17A/F-dependent immunity at mucosal surfaces, whereas those of connective tissue disorders (CTDs) often impair the TGF-β-dependent homeostasis of connective tissues. The signaling pathways involved are incompletely understood. We report a three-generation family with an autosomal dominant (AD) combination of CMC and a previously undescribed form of CTD that clinically overlaps with Ehlers-Danlos syndrome (EDS). The patients are heterozygous for a private splice-site variant of MAPK8, the gene encoding c-Jun N-terminal kinase 1 (JNK1), a component of the MAPK signaling pathway. This variant is loss-of-expression and loss-of-function in the patients' fibroblasts, which display AD JNK1 deficiency by haploinsufficiency. These cells have impaired, but not abolished, responses to IL-17A and IL-17F. Moreover, the development of the patients' TH17 cells was impaired ex vivo and in vitro, probably due to the involvement of JNK1 in the TGF-β-responsive pathway and further accounting for the patients' CMC. Consistently, the patients' fibroblasts displayed impaired JNK1- and c-Jun/ATF-2-dependent induction of key extracellular matrix (ECM) components and regulators, but not of EDS-causing gene products, in response to TGF-β. Furthermore, they displayed a transcriptional pattern in response to TGF-β different from that of fibroblasts from patients with Loeys-Dietz syndrome caused by mutations of TGFBR2 or SMAD3, further accounting for the patients' complex and unusual CTD phenotype. This experiment of nature indicates that the integrity of the human JNK1-dependent MAPK signaling pathway is essential for IL-17A- and IL-17F-dependent mucocutaneous immunity to Candida and for the TGF-β-dependent homeostasis of connective tissues.

Published
2019
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2. Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23

Author

Cindy S. Ma, Jean-Laurent Casanova, Monika Schmidt, Federico Mele, Gaspard Kerner, James P. Di Santo, Cecilia S. Lindestam Arlehamn, Avneet Heer, Lluis Quintana-Murci, Alessandro Sette, Bernhard Fleckenstein, Tomi Lazarov, Sandra Jovic, Natalie Wong, Stéphanie Boisson-Dupuis, Daniela Latorre, Julia K. Joseph, Bertrand Boisson, Rubén Martínez-Barricarte, Caner Aytekin, Danielle T. Avery, Aydan Ikinciogullari, Figen Dogu, Jean-François Emile, Etienne Patin, Federica Sallusto, Yoann Seeleuthner, Yuval Itan, Laurent Abel, Franck Rapaport, Alejandro Nieto-Patlán, Frederic Geissmann, Satoshi Okada, Fabienne Jabot-Hanin, Stuart G. Tangye, Esther van de Vosse, Geetha Rao, Elissa K. Deenick, Jacinta Bustamante, Mélanie Migaud, Caroline Deswarte, Mohammed Reza Bloursaz, Laura Surace, Benedetta Bigio, Davood Mansouri, Anne Puel, Payam Tabarsi, Xiao-Fei Kong, Gönül Tanır, Vanessa L. Bryant, Noé Ramírez-Alejo, Seyed Alireza Mahdaviani, Janet Markle, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], University of New South Wales [Sydney] (UNSW), Università della Svizzera italiana = University of Italian Switzerland (USI), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Sami Ulus Maternity and Children Training and Research Hospital, The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, The Royal Melbourne Hospital, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Génomique évolutive, modélisation et santé (GEMS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique Evolutive Humaine - Human Evolutionary Genetics, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Hiroshima University, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Ankara University School of Medicine [Turkey], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], King‘s College London, La Jolla Institute for Immunology [La Jolla, CA, États-Unis], University of California [San Diego] (UC San Diego), University of California (UC), Hôpital Ambroise Paré [AP-HP], Leiden University Medical Center (LUMC), Universiteit Leiden, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), The Laboratory of Human Genetics of Infectious Diseases was supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID) grant numbers 5R37AI095983, R01AI089970, and K99AI127932, the National Center for Research Resources and the National Center for Advancing Sciences (NCATS) of the NIH grant number UL1TR001866, the Rockefeller University, the St. Giles Foundation, the European Research Council (ERC-2010-AdG-268777 and grant no. 323183), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris Descartes University, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), and the French National Research Agency (ANR) under the 'Investissement d’avenir' program (grant ANR-10-IAHU-01), ANR-TBPATHGEN (grant ANR-14-CE14-0007-01), ANR-IFNPHOX (grant ANR13-ISV3-0001-01), and ANR-GENMSMD (grant ANR16-CE17-0005-01). This work was supported by NIAID award no. U19AI118626 (to A.S. and F.S.). J.G.M. was funded by the Canadian Institutes of Health Research, the NIH Translational Science Award (CTSA) program (no. UL1 TR000043), the Swiss National Science Foundation (grant no. IZKOZ3_173586), the Charles H. Revson Foundation, and the NIAID (1K99AI127932-01A1). R.M.-B. was supported by the European Molecular Biology Organization (EMBO). N.R.-A. was supported by the National Council of Science and Technology of Mexico (CONACYT, 264011) and the Stony Wold-Herbert Fund Fellowship Grant. Y.I. was supported by the AXA Research Fund. S.G.T., E.K.D., and C.S.M. are supported by research grants and fellowships from the National Health and Medical Research Council of Australia (S.G.T., C.S.M., and E.K.D.) and the Office for Health and Medical Research of the State Government of NSW Australia (C.S.M.). A.S. is supported by NIH research grant HHSN272200900044C. J.B. is supported by SRC2017. The Institute for Research in Biomedicine and F.S. are supported by the Helmut Horten Foundation. S.O. was supported by the Aid for Scientific Research Grant from the Japanese Society for the Promotion of Science (16H05355) and the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-14-CE14-0007,TBPATHGEN,Dissection de la pathogenèse de la tuberculose par l'identification de défauts monogéniques de l'immunité dans les formes pédiatriques sévères de la maladie(2014), ANR-13-ISV3-0001,IFNGPHOX,L'immunité anti-tuberculeuse dépendante de l'IFN-gamma chez l'homme opère via la NADPH oxydase phagocytaire(2013), ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), European Project: 268777,EC:FP7:ERC,ERC-2010-AdG_20100317,GENTB(2011), European Project: 323183,EC:FP7:ERC,ERC-2012-ADG_20120314,PREDICT(2013), Shahid Beheshti University, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique évolutive, modélisation et santé (CNRS-UMR2000), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of California, The Rockefeller University, St Giles laboratory of Human Genetics and Infectious Diseases, rockefeller university, Garvan Institute of Medical Research [Darlinghurst, Australia], Dis Training & Res Ctr, Shahid Beheshti University of Medical Sciences, Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Immunité Innée, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Centre de Bioinformatique (CBIO), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Sami Ulus Children Hlth & Dis Training & Res Ctr, Ankara, Génétique Humaine des Maladies Infectieuses (Inserm U980), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Service d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Univ Erlangen Nurnberg, La Jolla Institute for Allergy and Immunology, Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Garvan Institute for Medical Research, and Institute for Research in Biomedicine

Subjects
MESH: Interleukin-12, 0301 basic medicine, MESH: Interferon-gamma, MESH: Pedigree, medicine.medical_treatment, Immunology, Population, Mycobacterium Infections, Nontuberculous, Biology, Interleukin-23, Article, Mycobacterium, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, MESH: Mycobacterium, medicine, Humans, Interferon gamma, education, Interleukin 12 receptor, beta 1 subunit, MESH: Interleukin-23, education.field_of_study, MESH: Humans, General Medicine, MESH: Mycobacterium Infections, Nontuberculous, Natural killer T cell, Interleukin-12, Immunity, Innate, Pedigree, 3. Good health, 030104 developmental biology, Cytokine, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Interleukin 12, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, 030215 immunology, medicine.drug
Abstract

International audience; Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rβ1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL-12-dependent IFN-γ immunity and IL-23-dependent IL-17A/IL-17F immunity, respectively. We report here patients with autosomal recessive, complete IL-12Rβ2 or IL-23R deficiency, lacking responses to IL-12 or IL-23 only, all of whom, unexpectedly, display mycobacteriosis without candidiasis. We show that αβ T, γδ T, B, NK, ILC1, and ILC2 cells from healthy donors preferentially produce IFN-γ in response to IL-12, whereas NKT cells and MAIT cells preferentially produce IFN-γ in response to IL-23. We also show that the development of IFN-γ-producing CD4 + T cells, including, in particular , mycobacterium-specific TH1* cells (CD45RA− CCR6+), is dependent on both IL-12 and IL-23. Last, we show that IL12RB1, IL12RB2, and IL23R have similar frequencies of deleterious variants in the general population. The comparative rarity of symptomatic patients with IL-12Rβ2 or IL-23R deficiency, relative to IL-12Rβ1 deficiency , is, therefore, due to lower clinical penetrance. There are fewer symptomatic IL-23R-and IL-12Rβ2-deficient than IL-12Rβ1-deficient patients, not because these genetic disorders are rarer, but because the isolated absence of IL-12 or IL-23 is, in part, compensated by the other cytokine for the production of IFN-γ, thereby providing some protection against mycobacteria. These experiments of nature show that human IL-12 and IL-23 are both required for optimal IFN-γ dependent immunity to mycobacteria, both individually and much more so cooperatively.

Published
2018
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3. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations

Author

Jean-Pierre de Villartay, Luigi D. Notarangelo, Caroline Deswarte, Danielle T. Avery, Rubén Martínez-Barricarte, Masao Kobayashi, Claire Soudais, Dina Averbuch, Fabienne Jabot-Hanin, Egídio Torrado, Chizuru Okada, Stuart G. Tangye, Yuval Itan, Despina Moshous, Bertrand Boisson, Cindy S. Ma, Anne Puel, M. Lagos, Capucine Picard, Mohammed Alzahrani, Jamie Rossjohn, Rabih Halwani, Elissa K. Deenick, Jeffrey J. Fountain, Jamal Shamma, Jacinta Bustamante, Mélanie Migaud, Natalie Wong, Dan Engelhard, Daniela Latorre, Aziz Belkadi, Sylvain Breton, Sylvain Latour, Federico Mele, Janet Markle, Marcela Gonzalez, Hiyam Marzouqa, Sophie Hambleton, Stéphanie Boisson-Dupuis, Laurent Abel, James McCluskey, Federica Sallusto, Alessandro Sette, Peter D. Arkwright, Saleh Al-Muhsen, Olivier Lantz, Jean-Laurent Casanova, Lauren A. Henderson, Andrea M. Cooper, Cecilia S. Lindestam Arlehamn, and Satoshi Okada

Subjects
0303 health sciences, Multidisciplinary, biology, T cell, Gene rearrangement, Mucocutaneous Candidiasis, medicine.disease, biology.organism_classification, Chronic Candidiasis, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, RAR-related orphan receptor gamma, Immunity, Immunology, medicine, Chronic mucocutaneous candidiasis, Candida albicans, 030304 developmental biology, 030215 immunology
Abstract

A surprising immune twist for RORC The immune system needs its full array of soldiers—including cells and the molecules they secrete—to optimally protect the host. When this isn't the case, minor infections can become chronic or even deadly. Markle et al. report the discovery of seven individuals carrying loss-of-function mutations in RORC, which encodes the transcription factors RORγ and RORγT. These individuals lacked immune cells that produce the cytokine interleukin-17, causing them to suffer from chronic candidiasis. RORC-deficient individuals also exhibited impaired immunity to mycobacterium, probably due to reduced production of the cytokine interferon-γ, a molecule not known to require RORC for its induction. Science , this issue p. 606

Published
2015
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