Gpr15, an orphan G protein-coupled receptor, was initially recognized as a co-receptor for HIV-1 and 2 on lymphocytes. It also serves as a chemoattractant receptor, playing a central role in immune homeostasis and inflammation by guiding leukocyte migration. It has been linked to pathways related to T-cell trafficking in the intestinal epithelium and is crucial for maintaining immune balance in the gut [1,2,4]. Genetic models, such as gene knockout (KO) mouse models, have been instrumental in studying its functions.

In KO mouse models, Gpr15 deficiency led to increased colonic polyps and lower survival in the AOM/DSS colitis-associated colon cancer model, with decreased CD8+ T cells and increased IL-17+ CD4+ and IL-17+ CD8+ T cells in colonic polyps, indicating its role in promoting a tumor-suppressive immune microenvironment in colon cancer [3]. In acute viral myocarditis, Gpr15-deficient mice showed impaired coxsackievirus B3 elimination, adverse cardiac remodeling and dysfunction due to delayed T-cell recruitment [5].

In conclusion, Gpr15 is essential for immune-related functions, especially in T-cell homing and immune homeostasis in various tissues. Studies using Gpr15 KO mouse models have revealed its significance in colon cancer and acute viral myocarditis, providing insights into the disease mechanisms and potential therapeutic targets.