PTU-010 Role for GPR15 rather than beta 7 integrins in the pathogenesis of autoimmune liver disease

IntroductionG protein-coupled receptor 15 (GPR15) is a chemoattractant receptor that directs homing of lymphocytes to the colon. Furthermore, it has been shown to be a mediator of effector T cell homing during intestinal inflammation. Evidence exists showing infiltration of gut derived α4β7+ and CCR9+ T cells in the hepatic infiltrate of patients with autoimmune liver disease (AILD), in particular primary sclerosing cholangitis (PSC), with expression of their complementary ligands also being identified on the hepatic endothelium. However, the role of GPR15 in hepatic gut T cell homing remains to be defined.MethodsExplanted liver tissue was collected from patients undergoing orthotopic liver transplantation for chronic liver disease (Alcoholic liver disease [ALD] n=3, Non-alcoholic fatty liver disease [NAFLD] n=3, PSC n=4) with healthy control tissue sourced from patients undergoing hepatocellular carcinoma (HCC) resection (n=4). Liver infiltrating lymphocytes (LIL) were isolated using a mechanical homogenisation and centrifugation/filtration technique. Expression of gut homing markers on T cells was quantified using flow cytometry.ResultsExpression of GPR15 was significantly increased on CD4+ effector T cells (CD4+ CD127+ CD45RO+) in NAFLD, ALD and PSC patients compared to healthy controls (9.7 ± 0.4, 12.7 ± 0.9 and 20.1 ± 1.8 vs 4.1 ± 1.8, P