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Oxysterol-EBI2 signaling in immune regulation and viral infection

Daugvilaite, Viktorija and Arfelt, Kristine and Benned-Jensen, Tau and Sailer, Andreas and Rosenkilde, Mette (2014) Oxysterol-EBI2 signaling in immune regulation and viral infection. European Journal of Immunology, 44. pp. 1904-1912.

Abstract

The 7TM G protein-coupled receptor EBI2 (GPR183) was identified in 1993 by its substantial upregulation in Epstein-Barr Virus (EBV) infected cells. It is primarily expressed in lymphoid cells; most abundantly in B lymphocytes. EBI2 is central for the positioning of B cells within the lymphoid organs, a process that is regulated in part by a chemotactic gradient formed by the endogenous lipid agonists, and in part by a fine-tuned regulation of EBI2 cell surface expression. The most potent endogenous agonist is 7a, 25-dihydroxyxcholesterol (7a,25-OHC), yet EBI2 binds many structurally related oxysterols in a pocket defined by the upper parts of the transmembrane helices and extracellular receptor regions. It signals via Gi and also G protein-independent pathways like b-arrestin recruitment. The concerted action of these pathways leads to cell migration. By using genetically engineered up- and down regulation, EBI2 was recently shown also to induce cell proliferation; an action that could be inhibited by small molecule antagonists. Here we focus on the EBI2/oxysterol axis in immune control, hereunder the role in the EBV lifecycle. We also summarize the structural and functional properties of EBI2 interaction with oxysterol agonists and small molecule antagonist and ultimately discuss the drugability of EBI2 for diseases within the immune system.

Item Type: Article
Keywords: EBI2; GPR183, oxysterol
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/20589

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