B3 - Role of regulatory T cells and TH17 cells for the pathogenesis and treatment of cholangitis
Prof. Dr. med. Christoph Schramm
I. Department of Internal Medicine
University Medical Center Hamburg-Eppendorf
Primary (PSC) and secondary sclerosing cholangitis often progresses to liver cirrhosis and end stage liver disease. This is due to inflammation and fibrosis at the mucosal barrier of bile ducts.
At this interface, immune reactions must be well balanced in order to limit inflammation but allow proper pathogen defence. Regulatory T cells (Treg) and IL-17 producing TH17 cells are key players in the regulation of mucosal immunity because they are involved both in the development of autoimmunity and in pathogen defence.
B3 in 60 SecondsVideoarchivonline seit 14.12.2012
In project B3 we aim to define the pathogenetic role of these cells for the development of experimental cholangitis and to investigate whether the modulation of Treg and TH17 cells could be used for the future treatment of primary and secondary forms of sclerosing cholangitis.
Schwinge D*, von Haxthausen F*, Quaas A, Carambia A, Otto B, Glaser F, Höh B, Thiele N, Schoknecht T, Huber S, Steffens N, Lohse AW, Herkel J, Schramm C
Dysfunction of hepatic regulatory T cells in experimental sclerosing cholangitis is related with IL-12 signaling
J Hepatol. 2016 Dec 10. pii:S0168-8278(16)30705-X. doi: 10.1016/j.jhep.2016.12.001. [Epub ahead of print]
*equally contributing authors
Schwinge D, Carambia A, Quaas A, Krech T, Wegscheid C, Tiegs G, Prinz I, Lohse AW, Herkel J, Schramm C
Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis
J Immunol. 2015 Mar 15;194(6):2522-30. doi: 10.4049/jimmunol.1400076. Epub 2015 Feb 11.
Sebode M, Peiseler M, Franke B, Schwinge D, Schoknecht T, Wortmann F, Quaas A, Petersen BS, Ellinghaus E, Baron U, Olek S, Wiegard C, Weiler-Normann C, Lohse AW, Herkel J, Schramm C
Reduced FOXP3+ regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms
J Hepatol. 2014 May;60(5):1010-6. doi: 10.1016/j.jhep.2013.12.027. Epub 2014 Jan 8.