Gpr15-KO Mouse

Gpr15, a G protein-coupled receptor, was initially known as a co-receptor for human immunodeficiency virus (HIV) types 1 and 2. It is involved in multiple biological functions such as regulating innate immunity, T-cell trafficking in the intestinal epithelium, and maintaining immune homeostasis. It also serves as a colon-homing receptor for T cells and is part of the GPR15-C10orf99 signaling axis controlling intestinal homeostasis and inflammation [1,3].

In diet-related studies, dietary L-Tryptophan consumption determines the transcription level of Gpr15, affecting the number of colonic FOXP3+ regulatory T (Treg) cells. Two-week L-Trp supplementation nearly doubles colonic Gpr15+ Treg cells via Gpr15-mediated homing and reduces the risk of colitis [2]. In colon cancer, human CRC tissue analysis shows a reduction in Gpr15+ immune cell frequencies in tumors. Gpr15-deficient (KO) mice in the AOM/DSS colitis-associated colon cancer model have increased colonic polyps and lower survival, with decreased CD8+ T cells and increased IL-17+ CD4+ and IL-17+ CD8+ T cells in polyps. Administration of GPR15L to established tumors in the MC38-CRC model increases CD45+ cell infiltration, enhances TNFα expression on CD4+ and CD8+ T cells, and reduces tumor burden [4]. In acute viral myocarditis, Gpr15 deficiency impairs coxsackievirus B3 elimination, leading to adverse cardiac remodeling and dysfunction due to delayed T-cell recruitment [5].

In conclusion, Gpr15 plays essential roles in various biological processes, especially in the immune system and intestinal-related functions. Gene knockout (KO) mouse models have been crucial in revealing its functions in diseases such as colitis, colon cancer, and acute viral myocarditis, providing insights into potential therapeutic targets for these conditions.