Gpr183, also known as Epstein-Barr virus-induced gene 2, is a G-protein-coupled receptor for oxysterols and hydroxylated metabolites of cholesterol. It plays pleiotropic roles in lipid metabolism, immune responses, and cell migration. Oxysterols, like 7α,25-dihydroxycholesterol (7α,25-OHC), act as its ligands, and the GPR183-oxysterol axis is involved in various biological processes such as immune cell positioning in secondary lymphoid tissues [2,4].

In murine models, loss-of-function mutation of Gpr183 has shown significant impacts. In influenza A virus and SARS-CoV-2 infection models, it reduced macrophage infiltration and inflammatory cytokine production in the lungs, attenuating disease severity [1]. In ILC3-related colitis models, Gpr183 inactivation decreased colitis severity and reduced the accumulation of intestinal lymphoid tissue [3]. In hypertension models, endothelial-specific deficiency of Gpr183 alleviated cardiovascular and renal injuries by regulating endothelial senescence [2].

In conclusion, Gpr183 is crucial in regulating immune responses, cell migration, and tissue homeostasis. Gene knockout mouse models have revealed its roles in severe viral respiratory infections, colitis, hypertension, and other diseases. These findings suggest that targeting Gpr183 could be a potential therapeutic strategy for these disease areas.

References:

1. Foo, Cheng Xiang, Bartlett, Stacey, Chew, Keng Yih, Short, Kirsty R, Ronacher, Katharina. 2023. GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection. In The European respiratory journal, 61, . doi:10.1183/13993003.01306-2022. https://pubmed.ncbi.nlm.nih.gov/36396144/

2. Chu, Qingqing, Li, Yujia, Wu, Jichao, Wang, Xiaojie, Yi, Fan. 2024. Oxysterol Sensing Through GPR183 Triggers Endothelial Senescence in Hypertension. In Circulation research, 135, 708-721. doi:10.1161/CIRCRESAHA.124.324722. https://pubmed.ncbi.nlm.nih.gov/39176657/

3. Misselwitz, Benjamin, Wyss, Annika, Raselli, Tina, Pot, Caroline, Pabst, Oliver. 2021. The oxysterol receptor GPR183 in inflammatory bowel diseases. In British journal of pharmacology, 178, 3140-3156. doi:10.1111/bph.15311. https://pubmed.ncbi.nlm.nih.gov/33145756/

4. Kjær, Viktoria M S, Daugvilaite, Viktorija, Stepniewski, Tomasz M, Selent, Jana, Rosenkilde, Mette M. 2023. Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization. In Science signaling, 16, eabl4283. doi:10.1126/scisignal.abl4283. https://pubmed.ncbi.nlm.nih.gov/37014928/