Project Details
KFO 306: Primär Sklerosierende Cholangitis
Subject Area
Medicine
Term
from 2016 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 278045702
Primary Sclerosing Cholangitis (PSC) is a relatively rare, chronic progressive disease of bile ducts which leads to liver cirrhosis and cholangiocarcinoma. To date there is no effective therapy to alter the progressive course of disease. Patient survival is limited by the high risk of cirrhosis as well as hepatobiliary malignancy, but in addition health related quality of life is often impaired by PSC-associated complications such as osteoporosis.PSC is characterized by inflammation and fibrosis of intra- and/or extrahepatic bile ducts and by its strong association with inflammatory bowel disease, most often PSC-asssociated pancolitis. These disease features underline the importance of the mucosal surface for disease pathogenesis. In recent years it has become clear that the microbiome is critical for the maintenance and breach of mucosal immune homeostasis. Within the CRU306 we hypothesize that the microbiome and its associated immunological and metabolic changes determine disease pathogenesis and course. In previous work we could show that PSC is associated with changes in intestinal microbiota composition, which were validated across geographical regions, and recently also with changes in the biliary microbiota. We have shown that PSC is associated with altered immune cell populations in blood and liver and that T cells from patients with PSC showed increased pro-inflammatory cytokine production after stimulation with heat-inactivated bacteria. The CRU306 brings together a number of clinical and basic science experts in hepatology, immunology, microbiome research and bioinformatics. In the next funding period we will focus on the functional meaning of the observed changes in PSC-associated microbiota, immunological and metabolic patterns with regard to disease pathogenesis, phenotype and disease course in humans and respective mouse models.
DFG Programme
Clinical Research Units
Projects
- Analysis of the connection between inflammatory bowel disease and primary sclerosing cholangitis (PSC) (Applicant Huber, Samuel )
- Central Project (Applicant Lohse, Ansgar W. )
- Coordination Funds (Applicant Schramm, Christoph )
- Gut bacteria-derived Metabolites and their Impact on the Pathogenesis of Primary Sclerosing Cholangitis (Applicant Heeren, Jörg )
- IFNy-dependent immune responses are involved in the pathogenesis of PSC (Applicant Tiegs, Gisa )
- Inflammatory processes in the development of cholangiocarcinoma in Primary Sclerosing Cholangitis – Do the T cells play a role? (Applicant Gagliani, Ph.D., Nicola )
- Influence of PSC on skeletal remodeling (Applicants Amling, Michael ; Schinke, Ph.D., Thorsten )
- Innate immune cells in the pathogenesis of PSC (Applicants Altfeld, Marcus ; Herkel, Johannes )
- Neutrophil Extracellular Traps in the pathogenesis of PSC (Applicant Renné, Thomas )
- Project P-C: Disease modelling with the PSC Integrative Data Environment (PrIDE) (Applicant Bonn, Stefan )
- The intestinal and biliary microbiome in Primary Sclerosing Cholangitis (PSC) (Applicants Franke, Andre ; Schramm, Christoph )
Spokesperson
Professor Dr. Ansgar W. Lohse
Project Heads
Professor Dr. Marcus Altfeld; Professor Dr. Michael Amling; Dr. Roja Barikbin; Tanja Bedke, Ph.D.; Professor Dr. Stefan Bonn; Professor Dr. Andre Franke; Dr. Tobias Fuchs; Professor Nicola Gagliani, Ph.D.; Professor Dr. Jörg Heeren; Professor Dr. Johannes Herkel; Professor Dr. Samuel Huber; Privatdozent Dr. Harald Ittrich; Professor Thorsten Schinke, Ph.D.; Professorin Dr. Gisa Tiegs; Dr. Christina Weiler-Normann; Privatdozent Dr. Jin Yamamura