B9 Signalling pathways involved in the induction and function of myeloid-derived suppressor cells in liver inflammation

Principal Investigator:

Prof. Linda Diehl, Ph.D.
Department of Experimental Immunology and Hepatology
University Medical Center Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Germany
Phone: +49-40-7410-58733
Fax: +49-40-7410-57150
E-Mail: li.diehl@uke.de

Participating staff:
Dr. rer. nat. Jessica Endig – PostDoc

Project description

Chronic inflammation is a common effector and driver of liver disease, as it causes liver fibrosis and cirrhosis, and is the most common cause of hepatocellular carcinoma. Several immune-regulatory mechanisms are at play to prevent chronic hepatitis from causing liver damage and to maintain liver function.

B9 in 60 SecondsVideoarchiv

online seit 01.01.1970

We have found that one key mechanism of immune regulation during chronic hepatic inflammation is the induction of so-called myeloid-derived suppressor cells (MDSC), which can dampen liver fibrosis via the inhibition of other immune cells infiltrating the inflamed liver. In our previous work we could identify an enzyme that may influence the development of such MDSC via the regulation of the eicosanoid Prostaglandin E2.

The goal of this project is to elucidate the molecular mechanisms underlying MDSC immune regulation in chronic hepatic inflammation. In particular we will be focussing on the role of this enzyme regulation PGE2 on the development of chronic hepatic inflammation in the context of a western diet. We aim to elucidate the molecular mechanisms important for immune regulatory function of MDSC and will probe whether environmental influences (like dietary or microbial stimuli) affect MDSC biology.

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Horst AK, Wegscheid C, Schaefers C, Schiller B, Neumann K, Lunemann S, Langeneckert AE, Oldhafer KJ, Weiler-Normann C, Lang KS, Singer BB, Altfeld M, Diehl L, Tiegs G.

Carcinoembryonic antigen-related cell adhesion molecule 1controls IL-2-dependent regulatory T-cell induction in immune-mediated hepatitis in mice.
Hepatology. 2018 Jan 29. doi: 10.1002/hep.29812. [Epub ahead of print]

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

Höchst B, Mikulec J, Baccega T, Metzger C, Welz M, Peusquens J, Tacke F, Knolle P, Kurts C, Diehl L, Ludwig-Portugall I

Differential induction of Ly6G and Ly6C positive myeloid derived suppressor cells in chronic kidney and liver inflammation and fibrosis
PLoS One. 2015 Mar 4;10(3):e0119662. doi: 10.1371/journal.pone.0119662. eCollection 2015

Höchst B, Schildberg FA, Sauerborn P, Gäbel YA, Gevensleben H, Goltz D, Heukamp LC, Türler A, Ballmaier M, Gieseke F, Müller I, Kalff J, Kurts C, Knolle PA, Diehl L

Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion
J Hepatol. 2013 Sep;59(3):528-35. doi: 10.1016/j.jhep.2013.04.033. Epub 2013 May 9