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 is involved in multiple biological processes such as immune cell positioning, organ development, and tissue homeostasis [3,6]. Oxysterols, like 7α,25-dihydroxycholesterol (7α,25-OHC), bind to Gpr183, and the receptor-ligand pair is associated with various diseases [6].

Loss-of-function mutation of Gpr183 in mice has shown significant impacts. In influenza A virus and SARS-CoV-2 infections, it reduced macrophage infiltration and inflammatory cytokine production in the lungs, attenuating the severity of SARS-CoV-2 infection and viral loads [1]. In group 3 innate lymphoid cells (ILC3s), Gpr183 deficiency caused a defect in the formation of cryptopatches and isolated lymphoid follicles in the colon, affecting colonic lymphoid tissue development and colitis [2]. In endothelial-specific Gpr183 knockout mice, it alleviated cardiovascular and renal injuries in hypertensive mice by regulating endothelial senescence [3]. In IBD-related colitis models, Gpr183 inactivation reduced the severity of colitis in some models and strongly reduced the accumulation of intestinal lymphoid tissue [4]. In Mycobacterium tuberculosis infection, Gpr183-deficient mice had increased lung Mtb burden and dysregulated interferons during early infection [5].

In conclusion, Gpr183 is crucial in immune-related and disease-associated processes. Gene knockout mouse models have been instrumental in revealing its role in viral respiratory infections, colonic inflammation, hypertension-related complications, inflammatory bowel diseases, and mycobacterial infections. These findings suggest that targeting Gpr183 could be a potential therapeutic strategy for these diseases [1,2,3,4,5].