B1 - Regulation of immune-mediated liver injury

B1_April 2014

Principal Investigator:

Prof. Dr. rer. nat. Gisa Tiegs
Department of Experimental Immunology and Hepatology
University Medical Center Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Phone: +49-40-7410-58731
Fax: +49-40-7410-57150
E-Mail: g.tiegs@uke.de

Project description

Continuous exposure of the liver towards bacterial and food antigens seems to be responsible for the tolerogenic properties of this organ. Depending on its composition, the gut microbiome seems to affect immune-regulation in the liver, probably by induction of immune-regulatory cells.

Defects in immune-regulation and loss of tolerance seem to be responsible for liver inflammation and autoimmune liver disease. Identification of microbial components that affect the sensitivity for development of liver inflammation and its regulation might allow drawing conclusions for immune-regulatory mechanisms in the liver thereby providing novel targets for therapeutic intervention.

B1 in 60 SecondsVideoarchiv

online seit 05.05.2013
Figure 1: Tolerance induction in response to liver inflammation

This project aims to identify mechanisms of immune regulation and tolerance induction in response to liver inflammation. In a CD4+ T cell-dependent liver injury model inducible by concanavalin A (ConA) in mice we could show that tolerance towards ConA restimulation was mediated by CXCR3+Tbet+IL-10+ regulatory T cells (Tregs). In their function as one of the local non-professional antigen-presenting cell populations in the liver, hepatocytes seem to activate negative signals of T cell stimulation leading to induction of IL-10+Tregs.

In the second founding period we aim at investigating the impact of the gut microbiome on the induction of IL-10+Tregs in the liver thereby disclosing microbial conditions for sensitivity towards liver injury and tolerance induction. Moreover, negative regulators of T cell activation, such as DC-HIL, Ceacam1 and Notch ligands will be analyzed with respect to immune-regulation and effects on the gut microbiome and vice versa.

Related news:

Neumann K, Karimi K, Meiners J, Voetlause R, Steinmann S, Dammermann W, Lüth S, Asghari F, Wegscheid C, Horst AK, Tiegs G

A Proinflammatory Role of Type 2 Innate Lymphoid Cells in Murine Immune-Mediated Hepatitis
J Immunol. 2017 Jan 1;198(1):128-137.

Wegwitz F, Lenfert E, Gerstel D, von Ehrenstein L, Einhoff J, Schmidt G, Logsdon M, Brandner J, Tiegs G, Beauchemin N, Wagener C, Deppert W, Horst AK

CEACAM1 controls the EMT switch in murine mammary carcinoma in vitro and in vivo
Oncotarget. 2016 Sep 27;7(39):63730-63746. doi: 10.18632/oncotarget.11650

Horst AK, Neumann K, Diehl L, Tiegs G

Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells
Cell Mol Immunol. 2016 May;13(3):277-92. doi: 10.1038/cmi.2015.112. Epub 2016 Apr 4. Review