© Werner Kriegel
B02: Coordination of gut-liver communication by directed immune cell migration
A key step in the progression of liver or gut injury, regardless of its etiology, is the development of inflammation as a consequence of the recruitment of leukocytes from the circulation. The balance and retention of immune cell subsets in liver and gut determines whether injury resolves, persists or progresses to chronicity and fibrosis. As immune cells enter the enterohepatic circulation and hepatic diseases can develop as extra-intestinal manifestations of IBD, an immunological relation between the intestine and the liver is suggested.
Selective inhibition of immune cell migration has already reached clinical application in the treatment of inflammatory bowel disease. New strategies to inhibit the recruitment of harmful pro-inflammatory leukocytes might provide vital interventional tools for other diseases affected by the liver and gut axis.
Previously we have shown that the adhesion molecules b7 integrin and MAdCAM-1 (mucosal addressin cell-adhesion molecule-1) participate in the pathogenesis of gastrointestinal diseases including inflammatory bowel disease (IBD) and non-alcoholic steatohepatitis (NASH).
In this project we will
- explore how migratory routes of immune cells interconnect gut and liver in homeostasis and inflammation.
- will compare wildtype (WT)-mice and adhesion molecule-deficient mice in different models of chronic experimental hepatitis or colitis to reveal the impact of adhesion molecule-mediated immune cell migration on liver or gut inflammation.
- monitor disease progression and trafficking of immune cells from the healthy or inflamed gut to the healthy or inflamed liver.
- identify and verify adhesion molecule-dependent immune cells that propel the liver or gut towards an inflammatory state using adoptive cell transfers.
- translate data obtained in mice by analyzing human samples from patients with liver diseases such as NASH, primary sclerosing cholangitis.
Our study will contribute to a better understanding of immune cell adhesion pathways which is prerequisite for the development of strategies for the selective inhibition of inflammatory immune cells affecting the liver-gut axis.
