Current liver research: Hepatic Treg failure to suppress sclerosing cholangitis

16 Dezember 2016

Primary sclerosing cholangitis (PSC) is a chronic, autoimmune cholestatic liver disease. Currently, there is no medical treatment available with a proven effect on disease progression. Studies recently described a reduced number and possibly reduced function of regulatory T cells (Treg) in PSC patients. Treg are critically involved in the control of immune reactions – they maintain immune tolerance and suppress exaggerated reactions of the defence system. Treg expansion might therefore be a promising therapeutic approach in sclerosing cholangitis.

Graphical abstract Schwinge, von Haxthausen et al. 2016 (© 2016, Journal of Hepatology)

To test this hypothesis, CRC 841 scientists around Prof. Christoph Schramm, head of the project B3 Role of regulatory T cells and TH17 cells for the pathogenesis and treatment of cholangitis, explored whether the in vivo expansion of Treg could be used for the treatment of sclerosing cholangitis in mice. They successfully enriched regulatory T cells in the liver using injections with an antibody complex. However, although enriched Treg were mainly located in areas of inflammation, they had no impact on the severity of cholangitis. Hepatic Treg dysfunction could be linked to increased interleukin 12 (IL-12) signaling due to upregulation of the IL-12 receptor.

Accordingly, the scientists conclude that Treg expansion alone is not sufficient for a successful treatment of sclerosing cholangitis. They suggest that neutralisation of IL-12 should be considered as part of treatment strategies to improve the efficacy of Treg treatment in liver diseases. The results of the study have been published online on Dezember 10 in Journal of Hepatology.

Publication:

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

Further information:

For contact details and description of CRC project B3: Role of regulatory T cells and TH17 cells for the pathogenesis and treatment of cholangitis

Since the beginning of 2016, the German Research Foundation (DFG) supports at University Medical Center Hamburg-Eppendorf the clinical research unit 306 “Primary sclerosing cholangitis (PSC)”. This unit aims at completely decipering the pathogenesis of PSC in order to establish new therapeutic options: Clinical research unit 306