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1. The Src family kinases: distinct functions of c-Src, Yes, and Fyn in the liver

Author

Reinehr Roland, Sommerfeld Annika, and Häussinger Dieter

Subjects
apoptosis, bile acids, osmolarity, proliferation, Biology (General), QH301-705.5
Abstract

The Src family kinases Yes, Fyn, and c-Src play a pivotal role in regulating diverse liver functions such as bile flow, proteolysis, apoptosis, and proliferation and are regulated by anisoosmotic cell volume changes, death receptor ligands, and bile acids. For example, cell swelling leads to an integrin-sensed and focal adhesion kinase-mediated activation of c-Src-triggering choleresis, proteolysis inhibition, regulatory volume decrease via p38MAPK and proliferation via the activation of the epidermal growth factor receptor and extracellular regulated kinases 1 and 2. In contrast, hepatocyte shrinkage generates an almost instantaneous oxidative stress response that triggers the activation of c-Jun N-terminal kinase and the Src family kinases Fyn and Yes. Whereas Fyn activation mediates cholestasis, Yes triggers CD95 activation and apoptosis. This review will discuss the role of Src family kinases in the regulation of liver function with emphasis on their role in osmo-signaling and bile acid signaling.

Published
2013
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2. Paired associative stimulation demonstrates alterations in motor cortical synaptic plasticity in patients with hepatic encephalopathy

Author

Nikolov, Petyo, Baumgarten, Thomas J., Hassan, Shady Safwat, Füllenbach, Nur-Deniz, Kircheis, Gerald, Häussinger, Dieter, Jördens, Markus, Butz, Markus, Schnitzler, Alfons, and Groiss, Stefan J.

Subjects
Quantitative Biology - Neurons and Cognition
Abstract

Objective: Hepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. Methods: 23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. Results: MEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. Conclusion: Our study revealed reduced synaptic plasticity of the primary motor cortex in HE. Significance: Reduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients., Comment: number of pages: 33; number of tables: 1; number of figures: 5; References: 94

Published
2022
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4. Onwards and upwards: European Journal of Medical Research continues as an open access publication

Author

Busch Stefan and Häussinger Dieter

Subjects
Medicine
Abstract

Abstract The well-established European Journal of Medical Research has joined BioMed Central's portfolio of journals in January 2012, converting to the open access publishing model. Since its launch in 1995 the journal has been a print-only publication; from now on, it continues as an open access, online-only journal. The conversion to open access opens up the potential for the journal to become a leading, globally visible title in the field of general medicine over the coming years.

Published
2012
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5. Toponomics method for the automated quantification of membrane protein translocation

Author

Kubitz Ralf, Becker Martin, Mühlfeld Stefanie, Borbe Stefan, Domanova Olga, Häussinger Dieter, and Berlage Thomas

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Intra-cellular and inter-cellular protein translocation can be observed by microscopic imaging of tissue sections prepared immunohistochemically. A manual densitometric analysis is time-consuming, subjective and error-prone. An automated quantification is faster, more reproducible, and should yield results comparable to manual evaluation. The automated method presented here was developed on rat liver tissue sections to study the translocation of bile salt transport proteins in hepatocytes. For validation, the cholestatic liver state was compared to the normal biological state. Results An automated quantification method was developed to analyze the translocation of membrane proteins and evaluated in comparison to an established manual method. Firstly, regions of interest (membrane fragments) are identified in confocal microscopy images. Further, densitometric intensity profiles are extracted orthogonally to membrane fragments, following the direction from the plasma membrane to cytoplasm. Finally, several different quantitative descriptors were derived from the densitometric profiles and were compared regarding their statistical significance with respect to the transport protein distribution. Stable performance, robustness and reproducibility were tested using several independent experimental datasets. A fully automated workflow for the information extraction and statistical evaluation has been developed and produces robust results. Conclusions New descriptors for the intensity distribution profiles were found to be more discriminative, i.e. more significant, than those used in previous research publications for the translocation quantification. The slow manual calculation can be substituted by the fast and unbiased automated method.

Published
2011
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7. In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation

Author

Jensen, Björn-Erik Ole, Knops, Elena, Cords, Leon, Lübke, Nadine, Salgado, Maria, Busman-Sahay, Kathleen, Estes, Jacob D., Huyveneers, Laura E. P., Perdomo-Celis, Federico, Wittner, Melanie, Gálvez, Cristina, Mummert, Christiane, Passaes, Caroline, Eberhard, Johanna M., Münk, Carsten, Hauber, Ilona, Hauber, Joachim, Heger, Eva, De Clercq, Jozefien, Vandekerckhove, Linos, Bergmann, Silke, Dunay, Gábor A., Klein, Florian, Häussinger, Dieter, Fischer, Johannes C., Nachtkamp, Kathrin, Timm, Joerg, Kaiser, Rolf, Harrer, Thomas, Luedde, Tom, Nijhuis, Monique, Sáez-Cirión, Asier, Schulze zur Wiesch, Julian, Wensing, Annemarie M. J., Martinez-Picado, Javier, and Kobbe, Guido

Published
2023
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8. Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis

Author

Griess, Kerstin, Rieck, Michael, Müller, Nadine, Karsai, Gergely, Hartwig, Sonja, Pelligra, Angela, Hardt, Robert, Schlegel, Caroline, Kuboth, Jennifer, Uhlemeyer, Celina, Trenkamp, Sandra, Jeruschke, Kay, Weiss, Jürgen, Peifer-Weiss, Leon, Xu, Weiwei, Cames, Sandra, Yi, Xiaoyan, Cnop, Miriam, Beller, Mathias, Stark, Holger, Kondadi, Arun Kumar, Reichert, Andreas S., Markgraf, Daniel, Wammers, Marianne, Häussinger, Dieter, Kuss, Oliver, Lehr, Stefan, Eizirik, Decio, Lickert, Heiko, Lammert, Eckhard, Roden, Michael, Winter, Dominic, Al-Hasani, Hadi, Höglinger, Doris, Hornemann, Thorsten, Brüning, Jens C., and Belgardt, Bengt-Frederik

Published
2023
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10. Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by β-Catenin Mutations

Author

Adebayo Michael, Adeola O, Ko, Sungjin, Tao, Junyan, Moghe, Akshata, Yang, Hong, Xu, Meng, Russell, Jacquelyn O, Pradhan-Sundd, Tirthadipa, Liu, Silvia, Singh, Sucha, Poddar, Minakshi, Monga, Jayvir S, Liu, Pin, Oertel, Michael, Ranganathan, Sarangarajan, Singhi, Aatur, Rebouissou, Sandra, Zucman-Rossi, Jessica, Ribback, Silvia, Calvisi, Diego, Qvartskhava, Natalia, Görg, Boris, Häussinger, Dieter, Chen, Xin, and Monga, Satdarshan P

Subjects
Chronic Liver Disease and Cirrhosis, Liver Cancer, Genetics, Liver Disease, Cancer, Digestive Diseases, Rare Diseases, Acetates, Animals, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Proliferation, Cell Survival, Child, Child, Preschool, Disease Models, Animal, Female, Glutamate-Ammonia Ligase, Glutamine, Hepatocytes, Humans, Infant, Liver Neoplasms, Male, Mechanistic Target of Rapamycin Complex 1, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Phenols, Retrospective Studies, Sirolimus, TOR Serine-Threonine Kinases, Transfection, Wnt Signaling Pathway, beta Catenin, Wnt, beta-catenin, glutamine synthetase, hepatocellular cancer, liver tumor, mTOR, metabolic zonation, personalized medicine, precision therapy, tumor metabolism, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism
Abstract

Based on their lobule location, hepatocytes display differential gene expression, including pericentral hepatocytes that surround the central vein, which are marked by Wnt-β-catenin signaling. Activating β-catenin mutations occur in a variety of liver tumors, including hepatocellular carcinoma (HCC), but no specific therapies are available to treat these tumor subsets. Here, we identify a positive relationship between β-catenin activation, its transcriptional target glutamine synthetase (GS), and p-mTOR-S2448, an indicator of mTORC1 activation. In normal livers of mice and humans, pericentral hepatocytes were simultaneously GS and p-mTOR-S2448 positive, as were β-catenin-mutated liver tumors. Genetic disruption of β-catenin signaling or GS prevented p-mTOR-S2448 expression, while its forced expression in β-catenin-deficient livers led to ectopic p-mTOR-S2448 expression. Further, we found notable therapeutic benefit of mTORC1 inhibition in mutant-β-catenin-driven HCC through suppression of cell proliferation and survival. Thus, mTORC1 inhibitors could be highly relevant in the treatment of liver tumors that are β-catenin mutated and GS positive.

Published
2019

11. Das Hirsch-Institut für Tropenmedizin

Author

Häussinger, Dieter

Subjects
Tropical Medicine, Infection Medicine, Medical Faculty of Adama Science and Technology University, Asella Teaching Hospital, Etiology of Chronic Liver Disease, Chronic Liver Diseases, Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau, ESTHER-Initiative, Medicine: general issues, Infectious and contagious diseases
Abstract

Das Hirsch-Institut für Tropenmedizin (HITM) wurde 2013 als Außenstelle der Klinik für Gastroenterologie, Hepatologie und Infektiologie der Heinrich-Heine-Universität Düsseldorf unter Leitung von Professor Dieter Häussinger eröffnet. Das HITM dient dem Zweck des Wissenstransfers in den Bereichen Wissenschaft und Medizin, der Ausbildung von Ärzten sowie der Durchführung wissenschaftlicher Projekte im Bereich der Infektions- und Tropenmedizin.

Published
2022
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12. The Hirsch Institute of Tropical Medicine

Author

Häussinger, Dieter

Subjects
Tropical Medicine, Infection Medicine, Medical Faculty of Adama Science and Technology University, Asella Teaching Hospital, Etiology of Chronic Liver Disease, Chronic Liver Diseases, Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau, ESTHER-Initiative, Medicine: general issues, Infectious and contagious diseases
Abstract

In 2013, the Hirsch Institute of Tropical Medicine was officially inaugurated as a branch of the Department of Gastroenterology, Hepatology, and Infectious Diseases at Heinrich Heine University Düsseldorf under the direction of Professor Dieter Häussinger. The HITM serves as a place of scientific medical knowledge transfer, postgraduate medical training, and of conducting scientific projects relating to tropical medicine and infectious diseases.

Published
2022
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17. Acute cardiac side effects after COVID-19 mRNA vaccination: a case series

Author

Freise, Noemi F., Kivel, Milena, Grebe, Olaf, Meyer, Christian, Wafaisade, Bahram, Peiper, Matthias, Zeus, Tobias, Schmidt, Jan, Neuwahl, Judith, Jazmati, Danny, Luedde, Tom, Bölke, Edwin, Feldt, Torsten, Jensen, Björn Erik Ole, Bode, Johannes, Keitel, Verena, Haussmann, Jan, Tamaskovics, Balint, Budach, Wilfried, Fischer, Johannes C., Knoefel, Wolfram Trudo, Schneider, Marion, Gerber, Peter Arne, Pedoto, Alessia, Häussinger, Dieter, van Griensven, Martijn, Rezazadeh, Amir, Flaig, Yechan, Kirchner, Julian, Antoch, Gerald, Schelzig, Hubert, and Matuschek, Christiane

Published
2022
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18. Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection

Author

Fischer, Johannes C., Balz, Vera, Jazmati, Danny, Bölke, Edwin, Freise, Noemi F., Keitel, Verena, Feldt, Torsten, Jensen, Björn-Erik Ole, Bode, Johannes, Lüdde, Tom, Häussinger, Dieter, Adams, Ortwin, Schneider, E. Marion, Enczmann, Jürgen, Rox, Jutta M., Hermsen, Derik, Schulze-Bosse, Karin, Kindgen-Milles, Detlef, Knoefel, Wolfram Trudo, van Griensven, Martijn, Haussmann, Jan, Tamaskovics, Balint, Plettenberg, Christian, Scheckenbach, Kathrin, Corradini, Stefanie, Pedoto, Alessia, Maas, Kitti, Schmidt, Livia, Grebe, Olaf, Esposito, Irene, Ehrhardt, Anja, Peiper, Matthias, Buhren, Bettina Alexandra, Calles, Christian, Stöhr, Andreas, Gerber, Peter Arne, Lichtenberg, Artur, Schelzig, Hubert, Flaig, Yechan, Rezazadeh, Amir, Budach, Wilfried, and Matuschek, Christiane

Published
2022
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19. Hepatic encephalopathy

Author

Häussinger, Dieter, Dhiman, Radha K., Felipo, Vicente, Görg, Boris, Jalan, Rajiv, Kircheis, Gerald, Merli, Manuela, Montagnese, Sara, Romero-Gomez, Manuel, Schnitzler, Alfons, Taylor-Robinson, Simon D., and Vilstrup, Hendrik

Published
2022
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22. Granulocyte-colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: A multicenter randomized trial (GRAFT study)

Author

Engelmann, Cornelius, Herber, Adam, Franke, Annegret, Bruns, Tony, Reuken, Philipp, Schiefke, Ingolf, Zipprich, Alexander, Zeuzem, Stefan, Goeser, Tobias, Canbay, Ali, Berg, Christoph, Trebicka, Jonel, Uschner, Frank E., Chang, Johannes, Mueller, Tobias, Aehling, Niklas, Schmelzle, Moritz, Splith, Katrin, Lammert, Frank, Lange, Christian M., Sarrazin, Christoph, Trautwein, Christian, Manns, Michael, Häussinger, Dieter, Pfeiffenberger, Jan, Galle, Peter R., Schmiedeknecht, Anett, and Berg, Thomas

Published
2021
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23. Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis

Author

Reich, Maria, Spomer, Lina, Klindt, Caroline, Fuchs, Katharina, Stindt, Jan, Deutschmann, Kathleen, Höhne, Johanna, Liaskou, Evaggelia, Hov, Johannes R., Karlsen, Tom H., Beuers, Ulrich, Verheij, Joanne, Ferreira-Gonzalez, Sofia, Hirschfield, Gideon, Forbes, Stuart J., Schramm, Christoph, Esposito, Irene, Nierhoff, Dirk, Fickert, Peter, Fuchs, Claudia Daniela, Trauner, Michael, García-Beccaria, María, Gabernet, Gisela, Nahnsen, Sven, Mallm, Jan-Philipp, Vogel, Marina, Schoonjans, Kristina, Lautwein, Tobias, Köhrer, Karl, Häussinger, Dieter, Luedde, Tom, Heikenwalder, Mathias, and Keitel, Verena

Published
2021
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28. Bile Acids and TGR5 (Gpbar1) Signaling

Author

Keitel, Verena, Gertzen, Christoph G. W., Schäfer, Sven, Klindt, Caroline, Wöhler, Christina, Deutschmann, Kathleen, Reich, Maria, Gohlke, Holger, Häussinger, Dieter, Rozman, Damjana, editor, and Gebhardt, Rolf, editor

Published
2020
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30. Ammonium chloride reduces excitatory synaptic transmission onto CA1 pyramidal neurons of mouse organotypic slice cultures.

Author

Kleidonas, Dimitrios, Hilfiger, Louis, Lenz, Maximilian, Häussinger, Dieter, and Vlachos, Andreas

Subjects
CENTRAL nervous system, GLUTAMINE synthetase, MICROPHYSIOLOGICAL systems, AMMONIUM chloride, CEREBROSPINAL fluid, NEURAL transmission
Abstract

Acute liver dysfunction commonly leads to rapid increases in ammonia concentrations in both the serum and the cerebrospinal fluid. These elevations primarily affect brain astrocytes, causing modifications in their structure and function. However, its impact on neurons is not yet fully understood. In this study, we investigated the impact of elevated ammonium chloride levels (NH4Cl, 5 mM) on synaptic transmission onto CA1 pyramidal neurons in mouse organotypic entorhino-hippocampal tissue cultures. We found that acute exposure to NH4Cl reversibly reduced excitatory synaptic transmission and affected CA3-CA1 synapses. Notably, NH4Cl modified astrocytic, but not CA1 pyramidal neuron, passive intrinsic properties. To further explore the role of astrocytes in NH4 Clinduced attenuation of synaptic transmission, we used methionine sulfoximine to target glutamine synthetase, a key astrocytic enzyme for ammonia clearance in the central nervous system. Inhibition of glutamine synthetase effectively prevented the downregulation of excitatory synaptic activity, underscoring the significant role of astrocytes in adjusting excitatory synapses during acute ammonia elevation. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Measures of infection prevention and incidence of SARS-CoV-2 infections in cancer patients undergoing radiotherapy in Germany, Austria and Switzerland

Author

Matuschek, Christiane, Fischer, Johannes C., Combs, Stephanie E., Fietkau, Rainer, Corradini, Stefanie, Zänker, Kurt, Bölke, Edwin, Djiepmo-Njanang, Freddy-Joel, Tamaskovics, Balint, Fischer, Joachim E., Stuschke, Martin, Pöttgen, Christoph, Förster, Robert, Zwahlen, Daniel R., Papachristofilou, Alexandros, Ganswindt, Ute, Pelka, Rainer, Schneider, E. Marion, Feldt, Torsten, Jensen, Björn Erik Ole, Häussinger, Dieter, Knoefel, Wolfram Trudo, Kindgen-Milles, Detlef, Pedoto, Alessia, Grebe, Olaf, van Griensven, Martijn, Budach, Wilfried, and Haussmann, Jan

Published
2020
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35. Targeting FXR in Cholestasis

Author

Keitel, Verena, Dröge, Carola, Häussinger, Dieter, Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Rosenthal, Walter, Editorial Board Member, Wang, KeWei, Editorial Board Member, Fiorucci, Stefano, editor, and Distrutti, Eleonora, editor

Published
2019
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36. Bile Acid-Activated Receptors: GPBAR1 (TGR5) and Other G Protein-Coupled Receptors

Author

Keitel, Verena, Stindt, Jan, Häussinger, Dieter, Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Rosenthal, Walter, Editorial Board Member, Wang, KeWei, Editorial Board Member, Fiorucci, Stefano, editor, and Distrutti, Eleonora, editor

Published
2019
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37. Delayed skin reaction after mRNA-1273 vaccine against SARS-CoV-2: a rare clinical reaction

Author

Hoff, Norman-Philipp, Freise, Noemi F., Schmidt, Albrecht G., Firouzi-Memarpuri, Parnian, Reifenberger, Julia, Luedde, Tom, Bölke, Edwin, Meller, Stephan, Homey, Bernhard, Feldt, Torsten, Jensen, Björn Erik Ole, Keitel, Verena, Schmidt, Livia, Maas, Kitti, Haussmann, Jan, Tamaskovics, Balint, Budach, Wilfried, Fischer, Johannes C., Buhren, Bettina Alexandra, Knoefel, Wolfram Trudo, Schneider, Marion, Gerber, Peter Arne, Pedoto, Alessia, Häussinger, Dieter, Grebe, Olaf, van Griensven, Martijn, Braun, Stephan A., Salzmann, Stefan, Rezazadeh, Amir, and Matuschek, Christiane

Published
2021
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38. Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

Author

Fischer, Johannes C., Schmidt, Albrecht G., Bölke, Edwin, Uhrberg, Markus, Keitel, Verena, Feldt, Torsten, Jensen, Björn, Häussinger, Dieter, Adams, Ortwin, Schneider, E. Marion, Balz, Vera, Enczmann, Jürgen, Rox, Jutta, Hermsen, Derik, Schulze-Bosse, Karin, Kindgen-Milles, Detlef, Knoefel, Wolfram Trudo, van Griensven, Martijn, Haussmann, Jan, Tamaskovics, Balint, Plettenberg, Christian, Scheckenbach, Kathrin, Corradini, Stefanie, Pedoto, Alessia, Maas, Kitti, Schmidt, Livia, Grebe, Olaf, Esposito, Irene, Ehrhardt, Anja, Peiper, Matthias, Buhren, Bettina Alexandra, Calles, Christian, Stöhr, Andreas, Lichtenberg, Artur, Freise, Noemi F., Lutterbeck, Matthias, Rezazadeh, Amir, Budach, Wilfried, and Matuschek, Christiane

Published
2021
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39. Correction to: Informed consent and informed intervention: SARS‑CoV‑2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing

Author

Fischer, Johannes C., Schmidt, Albrecht G., Bölke, Edwin, Keitel, Verena, Feldt, Torsten, Jensen, Björn, Freise, Noemi F., Häussinger, Dieter, Schneider, E. Marion, Hermsen, Derik, Kindgen-Milles, Detlef, Knoefel, Wolfram Trudo, Haussmann, Jan, Tamaskovics, Balint, Plettenberg, Christian, Scheckenbach, Kathrin, Corradini, Stefanie, Rox, Jutta, Balz, Vera, Maas, Kitti, Schmidt, Livia, Grebe, Olaf, Ehrhardt, Anja, Gerber, Peter Arne, Peiper, Matthias, Buhren, Bettina Alexandra, Lichtenberg, Artur, Rezazadeh, Amir, Budach, Wilfried, and Matuschek, Christiane

Published
2021
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40. Informed consent and informed intervention: SARS-CoV-2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing

Author

Fischer, Johannes C., Schmidt, Albrecht G., Bölke, Edwin, Keitel, Verena, Feldt, Torsten, Jensen, Björn, Freise, Noemi F., Häussinger, Dieter, Schneider, E. Marion, Hermsen, Derik, Kindgen-Milles, Detlef, Knoefel, Wolfram Trudo, Haussmann, Jan, Tamaskovics, Balint, Plettenberg, Christian, Scheckenbach, Kathrin, Corradini, Stefanie, Rox, Jutta, Balz, Vera, Maas, Kitti, Schmidt, Livia, Grebe, Olaf, Ehrhardt, Anja, Gerber, Peter Arne, Peiper, Matthias, Buhren, Bettina Alexandra, Lichtenberg, Artur, Rezazadeh, Amir, Budach, Wilfried, and Matuschek, Christiane

Published
2021
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42. Norursodeoxycholic acid versus placebo in the treatment of non-alcoholic fatty liver disease: a double-blind, randomised, placebo-controlled, phase 2 dose-finding trial

Author

Vogel, Wolfgang, Aigner, Elmar, Datz, Christian, Tilg, Herbert, Gerken, Guido, Rust, Christian, Cordes, Hans-Jörg, Steib, Christian, Pathil-Warth, Anita, Prinz, MD, Christian, Lammert, Frank, Antoni, Christoph, Klausmann, Gerhard, Häussinger, Dieter, Zipprich, Alexander, Traussnigg, Stefan, Schattenberg, Jörn M, Demir, Münevver, Wiegand, Johannes, Geier, Andreas, Teuber, Gerlinde, Hofmann, Wolf Peter, Kremer, Andreas E, Spreda, Frank, Kluwe, Johannes, Petersen, Jörg, Boettler, Tobias, Rainer, Florian, Halilbasic, Emina, Greinwald, Roland, Pröls, Markus, Manns, Michael P, Fickert, Peter, and Trauner, Michael

Published
2019
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46. T‐cell STAT3 is required for the maintenance of humoral immunity to LCMV

Author

McIlwain, David R, Grusdat, Melanie, Pozdeev, Vitaly I, Xu, Haifeng C, Shinde, Prashant, Reardon, Colin, Hao, Zhenyue, Beyer, Marc, Bergthaler, Andreas, Häussinger, Dieter, Nolan, Garry P, Lang, Karl S, and Lang, Philipp A

Subjects
Immunization, Biodefense, Infectious Diseases, Emerging Infectious Diseases, Vaccine Related, Prevention, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Infection, Animals, Antibodies, Viral, B-Lymphocytes, Chronic Disease, Gene Expression, Immunity, Humoral, Immunoglobulin G, Immunophenotyping, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Mice, Knockout, STAT3 Transcription Factor, Signal Transduction, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Helper-Inducer, Virus Replication, Chronic infection, Humoral immunity, LCMV, STAT3, T follicular helper cells, Immunology
Abstract

STAT3 is a critical transcription factor activated downstream of cytokine signaling and is integral for the function of multiple immune cell types. Human mutations in STAT3 cause primary immunodeficiency resulting in impaired control of a variety of infections, including reactivation of latent viruses. In this study, we investigate how T-cell functions of STAT3 contribute to responses to viral infection by inducing chronic lymphocytic choriomeningitis virus (LCMV) infection in mice lacking STAT3 specifically in T cells. Although mice with conditional disruption of STAT3 in T cells were able to mount early responses to viral infection similar to control animals, including expansion of effector T cells, we found generation of T-follicular helper (Tfh) cells to be impaired. As a result, STAT3 T cell deficient mice produced attenuated germinal center reactions, and did not accumulate bone marrow virus specific IgG-secreting cells, resulting in failure to maintain levels of virus-specific IgG or mount neutralizing responses to LCMV in the serum. These effects were associated with reduced control of viral replication and prolonged infection. Our results demonstrate the importance of STAT3 in T cells for the generation of functional long-term humoral immunity to viral infections.

Published
2015

48. Herausgeber- und Autorenadressen

Author

Weihrauch, Thomas R., primary, Diener, Hans-Christoph, additional, Duyster, Justus, additional, Girndt, Matthias, additional, Hach-Wunderle, Viola, additional, Häussinger, Dieter, additional, Hoppe, Uta C., additional, Kirchmaier, Carl M., additional, Lode, Hartmut, additional, Märker-Hermann, Elisabeth, additional, Niederau, Christoph M., additional, Poralla, Thomas, additional, Rasche, Kurt, additional, Ruß, Martin, additional, Scherbaum, Werner A., additional, Schinzel, Helmut, additional, Schott, Matthias, additional, Stahlmann, Ralf, additional, Thürmann, Petra A., additional, Voltz, Raymond, additional, Weihrauch, Martin R., additional, Weihrauch, Thomas R., additional, Welz-Barth, Annette, additional, Wenzel, René R., additional, Windler, Eberhard, additional, Zander, Thomas, additional, Zyriax, B.-Chr., additional, Heinz, Jürgen, additional, Lobnig, Brigitte M., additional, Ostendorf, Benedikt C., additional, and Pillitteri, Daniele, additional

Published
2021
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