B9 Molecular mechanisms underlying the induction and function of myeloid-derived suppressor cells in chronic hepatic inflammation and fibrosis
Prof. Linda Diehl, Ph.D.
Department of Experimental Immunology and Hepatology
University Medical Center Hamburg-Eppendorf
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.
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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. Liver resident hepatic stellate cells seem to be central to the development of MDSC, which most likely are generated locally from pro-inflammatory myeloid cells attracted to the liver during inflammation.
The goal of this project is to elucidate the molecular mechanisms underlying MDSC immune regulation in chronic hepatic inflammation. We will investigate which factors determine MDSC development in the liver and whether this occurs as a consequence of inflammatory/fibrotic changes in the liver. We aim to elucidate the molecular mechanisms important for immuneregulatory function of MDSC and will probe whether environmental influences (like dietary or microbial stimuli) affect MDSC biology.
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