SFB 1700:  Immune regulation in the liver: from homeostasis to disease

• Subject Area: Medicine ; Chemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530990199

Liver and biliary diseases have been recognised by the European Commission as high-burden and under-researched medical conditions in Europe. Indeed, liver and biliary diseases are now the second leading cause of disablement and inability to work in Europe, imposing a substantial disease burden on patients and a major economic burden on healthcare systems and societies. Maintenance of a healthy tissue state by the immune system is particularly challenging in the liver owing to the multitude of (neo-) antigens derived from hepatic metabolism and signals derived from nutrition and intestinal microorganisms that reach the liver via the portal vein and via the mucosal surface of the biliary tract. As an aggressive immune response to all these antigens would cause severe tissue damage, the liver has evolved effective mechanisms to control inflammation and in-duce immune tolerance. However, hepatic immune tolerance might come at the expense of a survival benefit for cancer cells and hepatotropic viruses by preventing their recognition and elimination by the immune system. Our central hypothesis is that the regulation of immune responses is a key function of the liver that determines organismal health. We propose that faulty orchestration of cellular interaction and signal-ling within the hepatic microenvironment can lead either to immune-mediated inflammation and auto-immune disease, or to persistent infections and cancer. Understanding the mechanisms of hepatic immune regulation that govern the development of tolerance or immune activation will form the basis for targeted therapies to modulate immune responses in the liver and to cure these high-burden liver and biliary diseases. The proposed CRC will bring together clinician scientists, medical scientists and expert computational scientists. We will thus create an interdisciplinary and synergistic environment combining newest omics and imaging technologies with hepatological expertise, nurtured by our large and well-characterised patient cohorts, investigator-initiated clinical trials and the large number of human biosamples prospectively acquired in our biobank.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - Autoaggressive CD4+ T cells participate in autoimmune liver disease (Project Head Gagliani, Ph.D., Nicola )
• A02 - Antigen-independent mechanisms determining tissue damage in liver autoimmunity (Project Heads Dudek, Michael ;  Knolle, Percy Alexander )
• A03 - The role of TNF in the regulation of hepatic autoimmunity (Project Heads Adlung, Lorenz ;  Herkel, Johannes )
• A04 - Dictating hepatic immune responses through bile acid-scavenging macrophages (Project Heads Bosurgi, Ph.D., Lidia ;  Worthmann, Anna )
• A05 - T cells and cholangiocytes: an interaction that governs portal immune regulation and determines biliary inflammation (Project Head Schwinge, Dorothee )
• A06 - The role of short expressed peptides and cell type composition in autoimmune liver inflamma-tion (Project Heads Hübner, Norbert ;  Schramm, Christoph )
• A07 - Using functional genomics to decipher the impact of polymorphisms in the IL2RA locus and other primary sclerosing cholangitis risk loci (Project Heads Ellinghaus, Ph.D., David ;  Huber, Samuel )
• A08 - Spatial decoding of hepatic microenvironments to decipher, diagnose and stratify autoim-mune hepatitis (Project Heads Puelles, Ph.D., Victor G. ;  Sebode, Marcial ;  Zimmermann, Marina )
• B01 - Intestinal inflammation modulates liver immune responses (Project Heads Huber, Samuel ;  Kempski, Jan )
• B02 - The role of microbiota-specific T cells as inflammatory drivers of hepatic diseases (Project Heads Bacher, Petra ;  Bang, Corinna )
• B03 - The biliary mucosal interface in hepatic immune regulation (Project Head Schramm, Christoph )
• B04 - Innate lymphoid cell development and modulation of cholangiocytes in biliary atresia (Project Head Bunders, Ph.D., Madeleine )
• B05 - The role of infected hepatocytes in regulating intrahepatic immunity (Project Head Dandri, Maura )
• B06 - The tolerogenic microenvironment in the liver facilitates metastasis formation (Project Head Giannou, Ph.D., Anastasios )
• B07 - X-ray Fluorescence Imaging (XFI) of immune cells and soluble molecules in the liver (Project Heads Bosurgi, Ph.D., Lidia ;  Feliu, Neus ;  Grüner, Florian )
• INF - Central data- and biobank (Project Heads Sebode, Marcial ;  Ückert, Frank )
• SP01 - Discovering liver pathomechanisms via computational and statistical analysis support and train-ing (Project Heads Baumbach, Jan ;  Bonn, Stefan ;  Zolotareva, Ph.D., Olga )
• Z - Central tasks of the collaborative research centre (Project Head Schramm, Christoph )
• iRTGMGK - Academy for translational liver immunology (Project Heads Lohse, Ansgar W. ;  Schwinge, Dorothee )

• Applicant Institution: Universität Hamburg
• Participating Institution: Universitätsklinikum Hamburg-Eppendorf ; Zentrum für Innere Medizin ; I. Medizinische Klinik und Poliklinik; Max-Delbrück-Centrum für Molekulare Medizin (MDC)
• Participating University: Christian-Albrechts-Universität zu Kiel; Technische Universität München (TUM)
• Spokesperson: Professor Dr. Christoph Schramm