Gpr15-KO Mouse

Gpr15, a G protein-coupled receptor, was initially known as a co-receptor for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). It has since been found to play a crucial role in immune cell trafficking, especially T-cell homing to the large intestine, and is involved in maintaining immune homeostasis and regulating inflammation [1,2]. It functions as part of signaling axes, such as the GPR15-C10orf99 axis which controls intestinal homeostasis [2].

In Gpr15-deficient (KO) mice in the AOM/DSS colitis-associated colon cancer model, there were increased colonic polyps and lower survival compared to Gpr15-sufficient (Het) mice. The analysis of immune cell infiltrates in the polyps showed decreased CD8+ T cells and increased IL-17+ CD4+ and IL-17+ CD8+ T cells in KO mice, indicating a role of Gpr15 in promoting a tumor-suppressive immune microenvironment in colon cancer [3]. In acute viral myocarditis, Gpr15 deficiency impaired coxsackievirus B3 elimination, leading to adverse cardiac remodeling and dysfunction due to delayed T-cell recruitment and prolonged inflammatory response [4].

In conclusion, Gpr15 is essential for immune cell trafficking, especially T-cell homing to specific tissues. Gene knockout mouse models have revealed its significance in colon cancer development, where it promotes a tumor-suppressive immune microenvironment, and in acute viral myocarditis, where it facilitates virus elimination. These findings provide important insights into the role of Gpr15 in disease-related biological processes, suggesting its potential as a therapeutic target.

References:

1. Bauer, Mario. 2021. The Role of GPR15 Function in Blood and Vasculature. In International journal of molecular sciences, 22, . doi:10.3390/ijms221910824. https://pubmed.ncbi.nlm.nih.gov/34639163/

2. Okamoto, Yukari, Shikano, Sojin. 2023. Emerging roles of a chemoattractant receptor GPR15 and ligands in pathophysiology. In Frontiers in immunology, 14, 1179456. doi:10.3389/fimmu.2023.1179456. https://pubmed.ncbi.nlm.nih.gov/37457732/

3. Namkoong, Hong, Lee, Bomi, Swaminathan, Gayathri, Becker, Laren S, Habtezion, Aida. 2023. GPR15 in colon cancer development and anti-tumor immune responses. In Frontiers in oncology, 13, 1254307. doi:10.3389/fonc.2023.1254307. https://pubmed.ncbi.nlm.nih.gov/38074634/

4. Stoffers, Bastian, Wolf, Hanna, Bacmeister, Lucas, Westermann, Dirk, Lindner, Diana. 2023. GPR15-mediated T cell recruitment during acute viral myocarditis facilitated virus elimination and improved outcome. In Nature cardiovascular research, 3, 76-93. doi:10.1038/s44161-023-00401-z. https://pubmed.ncbi.nlm.nih.gov/39195892/