SFB 841:  Liver Inflammation: Infection, Immune Regulation and Consequences

• Subject Area: Medicine ; Biology
• Term: from 2010 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 80750187

• Final Report Year: 2023

Final Report Abstract

A variety of insults, in particular of infectious, metabolic, or autoimmune origin, can cause liver damage and liver inflammation, which is one of the most common medical conditions in the world. Resultant liver cirrhosis is one of the ten leading causes of death. Liver cancer is the most common inflammation-induced cancer in the world, and is now second only to lung cancer as the leading cause of cancer death. At the same time, as the central metabolic organ, the liver fulfils vital functions that need to be maintained even under stress and injury. Thus, the liver features several protective mechanisms, including its unique capacity to regenerate, or its distinctive ability to down-regulate inflammation. Although these features might provide an evolutionary advantage, they can become detrimental in specific situations, such as in infections that become chronic due to a dampened local immune response, or in liver cancer that can be initiated and promoted by the liver’s regenerative and tolerogenic capacity. The central hypothesis of the CRC 841 was that immune regulatory mechanisms in the liver determine the outcome of infectious and inflammatory insults to the liver, as well as the risk of malignant transformation. On the basis of a better understanding of the regulatory mechanisms, we wanted to enable specific therapeutic manipulations. In addition, understanding liver inflammation should provide further insight into general mechanisms of initiation, resolution and consequences of inflammation in health and disease. In bringing together scientists of different disciplines, the CRC 841 established a role model for organ-specific inflammation research at our university. Our multidisciplinary, yet unified and synergistic approach using both advanced mouse models and human disease samples enabled us to obtain several major achievements that also resulted in novel treatment approaches. 1) We have addressed the interrelation between the immune response to pathogens and the clinical disease course, uncovering various mechanisms accounting for chronic inflammation, abscess formation or fibrosis. These studies have contributed to the development of a now approved drug inhibitor of hepatitis B virus and hepatitis D virus infection, and a novel experimental T cell therapy providing clearance of hepatitis B virus infection. 2) We have obtained quantification and functional characterisation of regulatory T cells in the liver of patients with autoimmune diseases, and established TNF and IL-17 as key T effector cell-derived molecules in autoimmune hepatitis and primary sclerosing cholangitis, respectively, resulting in an on-going clinical study providing preliminary evidence for efficacy of anti-TNF as primary therapy in autoimmune hepatitis. 3) We have identified a major mechanism of hepatic immune tolerance exerted by liver sinusoidal endothelial cells, and developed a patented method for selective antigen-delivery to these cells, providing antigen-specific immune tolerance and effective treatment for autoimmune diseases. The approach has been further investigated in our innovative transfer project and is currently translated to clinical studies in several indications by our application partner ‘Topas Therapeutics’. 4) We have investigated the links between metabolism and inflammation, and uncovered miR122 and RORalpha as potential targets for treatment of steatohepatitis. 5) We have uncovered key factors linking liver inflammation with carcinogenesis, including IL-6 and IL-22 signalling, providing potential targets for treatment of liver cancer. In conclusion, we dare say that the CRC 841 has produced significant scientific insights and contributions to major biomedical problems resulting in novel therapies for important diseases.

Publications

• CXCR3 Deficiency Exacerbates Liver Disease and Abrogates Tolerance in a Mouse Model of Immune-Mediated Hepatitis. The Journal of Immunology, 186(9), 5284-5293.
  Erhardt, Annette; Wegscheid, Claudia; Claass, Benjamin; Carambia, Antonella; Herkel, Johannes; Mittrücker, Hans-Willi; Panzer, Ulf & Tiegs, Gisa
  
• RGB marking facilitates multicolor clonal cell tracking. Nature Medicine, 17(4), 504-509.
  Weber, Kristoffer; Thomaschewski, Michael; Warlich, Michael; Volz, Tassilo; Cornils, Kerstin; Niebuhr, Birte; Täger, Maike; Lütgehetmann, Marc; Pollok, Jörg-Matthias; Stocking, Carol; Dandri, Maura; Benten, Daniel & Fehse, Boris
  
• FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency. Journal of Hepatology, 57(1), 125-132.
  Peiseler, Moritz; Sebode, Marcial; Franke, Björn; Wortmann, Frederike; Schwinge, Dorothee; Quaas, Alexander; Baron, Udo; Olek, Sven; Wiegard, Christiane; Lohse, Ansgar W.; Weiler-Normann, Christina; Schramm, Christoph & Herkel, Johannes
  
• IL-6 Controls the Innate Immune Response against Listeria monocytogenes via Classical IL-6 Signaling. The Journal of Immunology, 190(2), 703-711.
  Hoge, Judith; Yan, Isabell; Jänner, Nathalie; Schumacher, Valéa; Chalaris, Athena; Steinmetz, Oliver M.; Engel, Daniel R.; Scheller, Jürgen; Rose-John, Stefan & Mittrücker, Hans-Willi
  
• Increased T helper type 17 response to pathogen stimulation in patients with primary sclerosing cholangitis. Hepatology, 58(3), 1084-1093.
  Katt, Janosch; Schwinge, Dorothee; Schoknecht, Tanja; Quaas, Alexander; Sobottka, Ingo; Burandt, Eike; Becker, Christoph; Neurath, Markus F.; Lohse, Ansgar W.; Herkel, Johannes & Schramm, Christoph
  
• Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis. Journal of Hepatology, 58(3), 529-534.
  Weiler-Normann, Christina; Schramm, Christoph; Quaas, Alexander; Wiegard, Christiane; Glaubke, Claudia; Pannicke, Nadine; Möller, Sina & Lohse, Ansgar W.
  
• The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. Journal of Hepatology, 58(5), 861-867.
  Volz, Tassilo; Allweiss, Lena; ḾBarek, Mounira Ben; Warlich, Michael; Lohse, Ansgar W.; Pollok, Jörg M.; Alexandrov, Alexander; Urban, Stephan; Petersen, Jörg; Lütgehetmann, Marc & Dandri, Maura
  
• Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism. Hepatology, 60(5), 1483-1493.
  Oehler, Nicola; Volz, Tassilo; Bhadra, Oliver D.; Kah, Janine; Allweiss, Lena; Giersch, Katja; Bierwolf, Jeanette; Riecken, Kristoffer; Pollok, Jörg M.; Lohse, Ansgar W.; Fehse, Boris; Petersen, Joerg; Urban, Stephan; Lütgehetmann, Marc; Heeren, Joerg & Dandri, Maura
  
• Reduced FOXP3+ regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms. Journal of Hepatology, 60(5), 1010-1016.
  Sebode, Marcial; Peiseler, Moritz; Franke, Björn; Schwinge, Dorothee; Schoknecht, Tanja; Wortmann, Frederike; Quaas, Alexander; Petersen, Britt-Sabina; Ellinghaus, Eva; Baron, Udo; Olek, Sven; Wiegard, Christiane; Weiler-Normann, Christina; Lohse, Ansgar W.; Herkel, Johannes & Schramm, Christoph
  
• TGF-β-dependent induction of CD4+CD25+Foxp3+ Tregs by liver sinusoidal endothelial cells. Journal of Hepatology, 61(3), 594-599.
  Carambia, Antonella; Freund, Barbara; Schwinge, Dorothee; Heine, Markus; Laschtowitz, Alena; Huber, Samuel; Wraith, David C.; Korn, Thomas; Schramm, Christoph; Lohse, Ansgar W.; Heeren, Joerg & Herkel, Johannes
  
• Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice. Journal of Hepatology, 62(6), 1349-1356.
  Carambia, Antonella; Freund, Barbara; Schwinge, Dorothee; Bruns, Oliver T.; Salmen, Sunhild C.; Ittrich, Harald; Reimer, Rudolph; Heine, Markus; Huber, Samuel; Waurisch, Christian; Eychmüller, Alexander; Wraith, David C.; Korn, Thomas; Nielsen, Peter; Weller, Horst; Schramm, Christoph; Lüth, Stefan; Lohse, Ansgar W.; Heeren, Joerg & Herkel, Johannes
  
• Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function. PLOS Pathogens, 12(11),e1005909.
  Mackroth, Maria Sophia; Abel, Annemieke; Steeg, Christiane; Schulze zur Wiesch, Julian & Jacobs, Thomas
  
• IL-23 prevents IL-13-dependent tissue repair associated with Ly6C lo monocytes in Entamoeba histolytica -induced liver damage. Journal of Hepatology, 64(5), 1147-1157.
  Noll, Jill; Helk, Elena; Fehling, Helena; Bernin, Hannah; Marggraff, Claudia; Jacobs, Thomas; Huber, Samuel; Pelczar, Penelope; Ernst, Thomas; Ittrich, Harald; Otto, Benjamin; Mittrücker, Hans-Willi; Hölscher, Christoph; Tacke, Frank; Bruchhaus, Iris; Tannich, Egbert & Lotter, Hannelore
  
• IL‐6 trans‐signaling is essential for the development of hepatocellular carcinoma in mice. Hepatology, 65(1), 89-103.
  Bergmann, Juri; Müller, Miryam; Baumann, Niklas; Reichert, Manuel; Heneweer, Carola; Bolik, Julia; Lücke, Karsten; Gruber, Sabine; Carambia, Antonella; Boretius, Susanne; Leuschner, Ivo; Becker, Thomas; Rabe, Björn; Herkel, Johannes; Wunderlich, F. Thomas; Mittrücker, Hans‐Willi; Rose‐John, Stefan & Schmidt‐Arras, Dirk
  
• Inflammation-Induced Expression and Secretion of MicroRNA 122 Leads to Reduced Blood Levels of Kidney-Derived Erythropoietin and Anemia. Gastroenterology, 151(5), 999-1010.e3.
  Rivkin, Mila; Simerzin, Alina; Zorde-Khvalevsky, Elina; Chai, Chofit; Yuval, Jonathan B.; Rosenberg, Nofar; Harari-Steinfeld, Rona; Schneider, Ronen; Amir, Gail; Condiotti, Reba; Heikenwalder, Mathias; Weber, Achim; Schramm, Christoph; Wege, Henning; Kluwe, Johannes; Galun, Eithan & Giladi, Hilla
  
• Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection. Nature Communications, 7(1).
  Labberton, Linda; Kenne, Ellinor; Long, Andy T.; Nickel, Katrin F.; Di Gennaro, Antonio; Rigg, Rachel A.; Hernandez, James S.; Butler, Lynn; Maas, Coen; Stavrou, Evi X. & Renné, Thomas
  
• Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1. Nature Immunology, 17(9), 1067-1074.
  Garcia-Beltran, Wilfredo F; Hölzemer, Angelique; Martrus, Gloria; Chung, Amy W; Pacheco, Yovana; Simoneau, Camille R; Rucevic, Marijana; Lamothe-Molina, Pedro A; Pertel, Thomas; Kim, Tae-Eun; Dugan, Haley; Alter, Galit; Dechanet-Merville, Julie; Jost, Stephanie; Carrington, Mary & Altfeld, Marcus
  
• Sequence variations in HCV core-derived epitopes alter binding of KIR2DL3 to HLA-C∗03:04 and modulate NK cell function. Journal of Hepatology, 65(2), 252-258.
  Lunemann, Sebastian; Martrus, Gloria; Hölzemer, Angelique; Chapel, Anais; Ziegler, Maja; Körner, Christian; Garcia Beltran, Wilfredo; Carrington, Mary; Wedemeyer, Heiner & Altfeld, Marcus
  
• A Proinflammatory Role of Type 2 Innate Lymphoid Cells in Murine Immune-Mediated Hepatitis. The Journal of Immunology, 198(1), 128-137.
  Neumann, Katrin; Karimi, Khalil; Meiners, Jana; Voetlause, Ruth; Steinmann, Silja; Dammermann, Werner; Lüth, Stefan; Asghari, Farahnaz; Wegscheid, Claudia; Horst, Andrea K. & Tiegs, Gisa
  
• A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury. The Journal of Immunology, 199(12), 4078-4090.
  Kleinschmidt, Dörte; Giannou, Anastasios D.; McGee, Heather M.; Kempski, Jan; Steglich, Babett; Huber, Francis Jessica; Ernst, Thomas Michael; Shiri, Ahmad Mustafa; Wegscheid, Claudia; Tasika, Elena; Hübener, Peter; Huber, Philipp; Bedke, Tanja; Steffens, Niklas; Agalioti, Theodora; Fuchs, Tobias; Noll, Jill; Lotter, Hannelore; Tiegs, Gisa; ... & Huber, Samuel
  
• Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis. Nature Medicine, 23(7), 839-849.
  Worthmann, Anna; John, Clara; Rühlemann, Malte C; Baguhl, Miriam; Heinsen, Femke-Anouska; Schaltenberg, Nicola; Heine, Markus; Schlein, Christian; Evangelakos, Ioannis; Mineo, Chieko; Fischer, Markus; Dandri, Maura; Kremoser, Claus; Scheja, Ludger; Franke, Andre; Shaul, Philip W & Heeren, Joerg
  
• Dysfunction of hepatic regulatory T cells in experimental sclerosing cholangitis is related to IL-12 signaling. Journal of Hepatology, 66(4), 798-805.
  Schwinge, Dorothee; von Haxthausen, Franziska; Quaas, Alexander; Carambia, Antonella; Otto, Benjamin; Glaser, Fabian; Höh, Benedikt; Thiele, Nina; Schoknecht, Tanja; Huber, Samuel; Steffens, Niklas; Lohse, Ansgar W.; Herkel, Johannes & Schramm, Christoph
  
• Hepatitis delta virus persists during liver regeneration and is amplified through cell division both in vitro and in vivo. Gut, 68(1), 150-157.
  Giersch, Katja; Bhadra, Oliver D; Volz, Tassilo; Allweiss, Lena; Riecken, Kristoffer; Fehse, Boris; Lohse, Ansgar W; Petersen, Joerg; Sureau, Camille; Urban, Stephan; Dandri, Maura & Lütgehetmann, Marc
  
• Host DNases prevent vascular occlusion by neutrophil extracellular traps. Science, 358(6367), 1202-1206.
  Jiménez-Alcázar, Miguel; Rangaswamy, Chandini; Panda, Rachita; Bitterling, Josephine; Simsek, Yashin J.; Long, Andy T.; Bilyy, Rostyslav; Krenn, Veit; Renné, Christoph; Renné, Thomas; Kluge, Stefan; Panzer, Ulf; Mizuta, Ryushin; Mannherz, Hans Georg; Kitamura, Daisuke; Herrmann, Martin; Napirei, Markus & Fuchs, Tobias A.
  
• IL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo. The Journal of Immunology, 198(3), 1130-1141.
  Brockmann, Leonie; Gagliani, Nicola; Steglich, Babett; Giannou, Anastasios D.; Kempski, Jan; Pelczar, Penelope; Geffken, Maria; Mfarrej, Bechara; Huber, Francis; Herkel, Johannes; Wan, Yisong Y.; Esplugues, Enric; Battaglia, Manuela; Krebs, Christian F.; Flavell, Richard A. & Huber, Samuel
  
• Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection. Journal of Clinical Investigation, 127(8), 3177-3188.
  Kah, Janine; Koh, Sarene; Volz, Tassilo; Ceccarello, Erica; Allweiss, Lena; Lütgehetmann, Marc; Bertoletti, Antonio & Dandri, Maura
  
• Metabolic Circuit Involving Free Fatty Acids, microRNA 122, and Triglyceride Synthesis in Liver and Muscle Tissues. Gastroenterology, 153(5), 1404-1415.
  Chai, Chofit; Rivkin, Mila; Berkovits, Liav; Simerzin, Alina; Zorde-Khvalevsky, Elina; Rosenberg, Nofar; Klein, Shiri; Yaish, Dayana; Durst, Ronen; Shpitzen, Shoshana; Udi, Shiran; Tam, Joseph; Heeren, Joerg; Worthmann, Anna; Schramm, Christoph; Kluwe, Johannes; Ravid, Revital; Hornstein, Eran; Giladi, Hilla & Galun, Eithan
  
• Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo. Gut, 67(3), 542-552.
  Allweiss, Lena; Volz, Tassilo; Giersch, Katja; Kah, Janine; Raffa, Giuseppina; Petersen, Joerg; Lohse, Ansgar W; Beninati, Concetta; Pollicino, Teresa; Urban, Stephan; Lütgehetmann, Marc & Dandri, Maura
  
• Carcinoembryonic antigen‐related cell adhesion molecule 1 controls IL‐2‐dependent regulatory T‐cell induction in immune‐mediated hepatitis in mice. Hepatology, 68(1), 200-214.
  Horst, Andrea Kristina; Wegscheid, Claudia; Schaefers, Christoph; Schiller, Birgit; Neumann, Katrin; Lunemann, Sebastian; Langeneckert, Annika E.; Oldhafer, Karl J.; Weiler‐Normann, Christina; Lang, Karl S.; Singer, Bernhard B.; Altfeld, Marcus; Diehl, Linda & Tiegs, Gisa
  
• Colitis Promotes a Pathological Condition of the Liver in the Absence of Foxp3+ Regulatory T Cells. The Journal of Immunology, 201(12), 3558-3568.
  Mathies, Franziska; Steffens, Niklas; Kleinschmidt, Doerte; Stuhlmann, Friederike; Huber, Francis J.; Roy, Urmi; Meyer, Thomas; Luetgehetmann, Marc; von Petersdorff, Mareike; Seiz, Oliver; Herkel, Johannes; Schramm, Christoph; Flavell, Richard A.; Gagliani, Nicola; Krebs, Christian; Panzer, Ulf; Abdullah, Zeinab; Strowig, Till; Bedke, Tanja & Huber, Samuel
  
• Interactions Between KIR3DS1 and HLA-F Activate Natural Killer Cells to Control HCV Replication in Cell Culture. Gastroenterology, 155(5), 1366-1371.e3.
  Lunemann, Sebastian; Schöbel, Anja; Kah, Janine; Fittje, Pia; Hölzemer, Angelique; Langeneckert, Annika E.; Hess, Leonard U.; Poch, Tobias; Martrus, Gloria; Garcia-Beltran, Wilfredo F.; Körner, Christian; Ziegler, Annerose E.; Richert, Laura; Oldhafer, Karl J.; Schulze zur Wiesch, Julian; Schramm, Christoph; Dandri, Maura; Herker, Eva & Altfeld, Marcus
  
• Liver infiltrating T cells regulate bile acid metabolism in experimental cholangitis. Journal of Hepatology, 71(4), 783-792.
  Glaser, Fabian; John, Clara; Engel, Bastian; Höh, Benedikt; Weidemann, Sören; Dieckhoff, Jan; Stein, Stephanie; Becker, Nathalie; Casar, Christian; Schuran, Fenja Amrei; Wieschendorf, Björn; Preti, Max; Jessen, Friederike; Franke, Andre; Carambia, Antonella; Lohse, Ansgar W.; Ittrich, Harald; Herkel, Johannes; Heeren, Joerg; ... & Schwinge, Dorothee
  
• T cell receptor grafting allows virological control of hepatitis B virus infection. Journal of Clinical Investigation, 129(7), 2932-2945.
  Wisskirchen, Karin; Kah, Janine; Malo, Antje; Asen, Theresa; Volz, Tassilo; Allweiss, Lena; Wettengel, Jochen M.; Lütgehetmann, Marc; Urban, Stephan; Bauer, Tanja; Dandri, Maura & Protzer, Ulrike
  
• TNF-Producing Th1 Cells Are Selectively Expanded in Liver Infiltrates of Patients with Autoimmune Hepatitis. The Journal of Immunology, 203(12), 3148-3156.
  Bovensiepen, Claudia S.; Schakat, Miriam; Sebode, Marcial; Zenouzi, Roman; Hartl, Johannes; Peiseler, Moritz; Li, Jun; Henze, Lara; Woestemeier, Anna; Schramm, Christoph; Lohse, Ansgar W.; Herkel, Johannes & Weiler-Normann, Christina
  
• Agonist of RORA Attenuates Nonalcoholic Fatty Liver Progression in Mice via Up-regulation of MicroRNA 122. Gastroenterology, 159(3), 999-1014.e9.
  Chai, Chofit; Cox, Bryan; Yaish, Dayana; Gross, Devora; Rosenberg, Nofar; Amblard, Franck; Shemuelian, Zohar; Gefen, Maytal; Korach, Amit; Tirosh, Oren; Lanton, Tali; Link, Henrike; Tam, Joseph; Permyakova, Anna; Ozhan, Gunes; Citrin, Jonathan; Liao, Haixing; Tannous, Mirna; Hahn, Michal; ... & Galun, Eithan
  
• Androgens predispose males to monocyte-mediated immunopathology by inducing the expression of leukocyte recruitment factor CXCL1. Nature Communications, 11(1).
  Sellau, Julie; Groneberg, Marie; Fehling, Helena; Thye, Thorsten; Hoenow, Stefan; Marggraff, Claudia; Weskamm, Marie; Hansen, Charlotte; Stanelle-Bertram, Stephanie; Kuehl, Svenja; Noll, Jill; Wolf, Vincent; Metwally, Nahla Galal; Hagen, Sven Hendrik; Dorn, Christoph; Wernecke, Julia; Ittrich, Harald; Tannich, Egbert; Jacobs, Thomas; ... & Lotter, Hannelore
  
• Monocytes as Potential Mediators of Pathogen‐Induced T‐Helper 17 Differentiation in Patients With Primary Sclerosing Cholangitis (PSC). Hepatology, 72(4), 1310-1326.
  Kunzmann, Lilly Kristin; Schoknecht, Tanja; Poch, Tobias; Henze, Lara; Stein, Stephanie; Kriz, Marvin; Grewe, Ilka; Preti, Max; Hartl, Johannes; Pannicke, Nadine; Peiseler, Moritz; Sebode, Marcial; Zenouzi, Roman; Horvatits, Thomas; Böttcher, Marius; Petersen, Britt‐Sabina; Weiler‐Normann, Christina; Hess, Leonard U.; Ahrenstorf, Annika Elise; ... & Schwinge, Dorothee
  
• Aryl Hydrocarbon Receptor Activity in Hepatocytes Sensitizes to Hyperacute Acetaminophen-Induced Hepatotoxicity in Mice. Cellular and Molecular Gastroenterology and Hepatology, 11(2), 371-388.
  Schuran, Fenja A.; Lommetz, Christoph; Steudter, Andreas; Ghallab, Ahmed; Wieschendorf, Björn; Schwinge, Dorothee; Zuehlke, Sebastian; Reinders, Joerg; Heeren, Joerg; Lohse, Ansgar W.; Schramm, Christoph; Herkel, Johannes & Carambia, Antonella
  
• Cell-autonomous hepatocyte-specific GP130 signaling is sufficient to trigger a robust innate immune response in mice. Journal of Hepatology, 74(2), 407-418.
  Schumacher, Neele; Yan, Karsten; Gandraß, Monja; Müller, Miryam; Krisp, Christoph; Häsler, Robert; Carambia, Antonella; Nofer, Jerzy-Roch; Bernardes, Joanna P.; Khouja, Mouhamad; Thomsen, Ilka; Chalupsky, Karel; Bolik, Julia; Hölscher, Christoph; Wunderlich, Thomas; Herkel, Johannes; Rosenstiel, Philip; Schramm, Christoph; Schlüter, Hartmut; ... & Schmidt-Arras, Dirk
  
• Failure of thymic deletion and instability of autoreactive Tregs drive autoimmunity in immune-privileged liver. JCI Insight, 6(6).
  Preti, Max; Schlott, Lena; Lübbering, David; Krzikalla, Daria; Müller, Anna-Lena; Schuran, Fenja A.; Poch, Tobias; Schakat, Miriam; Weidemann, Sören; Lohse, Ansgar W.; Weiler-Normann, Christina; Sebode, Marcial; Schwinge, Dorothee; Schramm, Christoph; Carambia, Antonella & Herkel, Johannes
  
• IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression. Journal of Hepatology, 74(4), 919-930.
  Stein, Stephanie; Henze, Lara; Poch, Tobias; Carambia, Antonella; Krech, Till; Preti, Max; Schuran, Fenja Amrei; Reich, Maria; Keitel, Verena; Fiorotto, Romina; Strazzabosco, Mario; Fischer, Lutz; Li, Jun; Müller, Luisa Marie; Wagner, Jonas; Gagliani, Nicola; Herkel, Johannes; Schwinge, Dorothee & Schramm, Christoph
  
• Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis. Journal of Experimental Medicine, 219(1).
  Bolik, Julia; Krause, Freia; Stevanovic, Marija; Gandraß, Monja; Thomsen, Ilka; Schacht, Sarah-Sophie; Rieser, Eva; Müller, Miryam; Schumacher, Neele; Fritsch, Jürgen; Wichert, Rielana; Galun, Eithan; Bergmann, Juri; Röder, Christian; Schafmayer, Clemens; Egberts, Jan-Hendrik; Becker-Pauly, Christoph; Saftig, Paul; Lucius, Ralph; ... & Schmidt-Arras, Dirk
  
• Nanoparticle‐mediated targeting of autoantigen peptide to cross‐presenting liver sinusoidal endothelial cells protects from CD8 T‐cell‐driven autoimmune cholangitis. Immunology, 162(4), 452-463.
  Carambia, Antonella; Gottwick, Cornelia; Schwinge, Dorothee; Stein, Stephanie; Digigow, Reinaldo; Şeleci, Muharrem; Mungalpara, Disha; Heine, Markus; Schuran, Fenja A.; Corban, Carlotta; Lohse, Ansgar W.; Schramm, Christoph; Heeren, Joerg & Herkel, Johannes
  
• Next‐Generation Immunosequencing Reveals Pathological T‐Cell Architecture in Autoimmune Hepatitis. Hepatology, 73(4), 1436-1448.
  Schultheiß, Christoph; Simnica, Donjete; Willscher, Edith; Oberle, Anna; Fanchi, Lorenzo; Bonzanni, Nicola; Wildner, Nils H.; Schulze Zur Wiesch, Julian; Weiler‐Normann, Christina; Lohse, Ansgar W. & Binder, Mascha
  
• Therapeutic shutdown of HBV transcripts promotes reappearance of the SMC5/6 complex and silencing of the viral genome in vivo. Gut, 71(2), 372-381.
  Allweiss, Lena; Giersch, Katja; Pirosu, Andrea; Volz, Tassilo; Muench, Robert C; Beran, Rudolf K; Urban, Stephan; Javanbakht, Hassan; Fletcher, Simon P; Lütgehetmann, Marc & Dandri, Maura
  
• HIF-1α modulates sex-specific Th17/Treg responses during hepatic amoebiasis. Journal of Hepatology, 76(1), 160-173.
  Groneberg, Marie; Hoenow, Stefan; Marggraff, Claudia; Fehling, Helena; Metwally, Nahla Galal; Hansen, Charlotte; Bruchhaus, Iris; Tiegs, Gisa; Sellau, Julie & Lotter, Hannelore
  
• Transcriptional Pattern Analysis of Virus-Specific CD8+ T Cells in Hepatitis C Infection: Increased Expression of TOX and Eomesodermin During and After Persistent Antigen Recognition. Frontiers in Immunology, 13(2022, 6, 6).
  Wildner, Nils H.; Walker, Andreas; Brauneck, Franziska; Ditt, Vanessa; Peine, Sven; Huber, Samuel; Haag, Friedrich; Beisel, Claudia; Timm, Joerg & Schulze zur Wiesch, Julian
  
• Combined hepatocellular-cholangiocarcinoma derives from liver progenitor cells and depends on senescence and IL-6 trans-signaling. J Hepatol. 2022;77:1631-1641.
  Rosenberg, Nofar; Van Haele, Matthias; Lanton, Tali; Brashi, Neta; Bromberg, Zohar; Adler, Hanan; Giladi, Hilla; Peled, Amnon; Goldenberg, Daniel S.; Axelrod, Jonathan H.; Simerzin, Alina; Chai, Chofit; Paldor, Mor; Markezana, Auerlia; Yaish, Dayana; Shemulian, Zohar; Gross, Dvora; Barnoy, Shanny; Gefen, Maytal; … & Galun, Eithan
  
• Multicytokine-producing CD4+ T cells characterize the livers of patients with NASH. JCI Insight, 8(1).
  Woestemeier, Anna; Scognamiglio, Pasquale; Zhao, Yu; Wagner, Jonas; Muscate, Franziska; Casar, Christian; Siracusa, Francesco; Cortesi, Filippo; Agalioti, Theodora; Müller, Simone; Sagebiel, Adrian; Konczalla, Leonie; Wahib, Ramez; Karstens, Karl-Frederick; Giannou, Anastasios D.; Duprée, Anna; Wolter, Stefan; Wong, Milagros N.; Mühlig, Anne K.; ... & Gagliani, Nicola
  
• Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22. Immunity, 56(1), 125-142.e12.
  Giannou, Anastasios D.; Kempski, Jan; Shiri, Ahmad Mustafa; Lücke, Jöran; Zhang, Tao; Zhao, Lilan; Zazara, Dimitra E.; Cortesi, Filippo; Riecken, Kristoffer; Amezcua Vesely, Maria Carolina; Low, Jun Siong; Xu, Hao; Kaffe, Eleanna; Garcia-Perez, Laura; Agalioti, Theodora; Yamada, Yoshito; Jungraithmayr, Wolfgang; Zigmond, Ehud; Karstens, Karl-Frederick; ... & Huber, Samuel