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The oxysterol receptor GPR183 in inflammatory bowel diseases

Misselwitz, Benjamin and Wyss, Annika and Raselli, Tina and Cerovic, Vuc and Sailer, Andreas and Krupka, Niklas and Ruiz, Florian and Pot, Caroline and Papst, Oliver (2020) The oxysterol receptor GPR183 in inflammatory bowel diseases. British Journal of Pharmacology. pp. 1-17. ISSN 14765381

Abstract

Immune cell trafficking is an important mechanism for the pathogenesis of inflammatory bowel disease (IBD). The oxysterol receptor GPR183 and its ligands, dihydroxylated oxysterols, can mediate positioning of immune cells including innate lymphoid cells. GPR183 has been mapped to an IBD risk locus, however another gene, Ubac2 is encoded on the reverse strand and associated with Behçet's disease, therefore the role of GPR183 as a genetic risk factor requires validation. GPR183 and production of its oxysterol ligands are up-regulated in human IBD and murine colitis. Gpr183 inactivation reduced severity of colitis in group 3 innate lymphoid cells-dependent colitis and in IL-10 colitis but not in dextran sodium sulphate colitis. Irrespectively, Gpr183 knockout strongly reduced accumulation of intestinal lymphoid tissue in health and all colitis models. In conclusion, genetic, translational and experimental studies implicate GPR183 in IBD pathogenesis and GPR183-dependent cell migration might be a therapeutic drug target for IBD.

Item Type: Article
Keywords: colitis EBI2 GPR183 inflammatory bowel diseases innate lymphoid cells oxysterols solitary intestinal lymphoid tissue Ubac2
Date Deposited: 18 May 2021 00:45
Last Modified: 18 May 2021 00:45
URI: https://oak.novartis.com/id/eprint/43059

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