Human GPR15 Deficiency Reveals CD8+ T Regulatory Cell-Macrophage Crosstalk in Intestinal Inflammation

Inflammatory bowel disease (IBD) causes lifelong suffering from gastrointestinal inflammation and dysfunction with severe complications including colon cancer. The disease is increasing in global prevalence, and current therapies are insufficient, highlighting an urgent need to understand its pathogenic mechanism. We reported multiple patients with GPR15 deficiency which result in severe early-onset IBD. GPR15, a G protein-coupled receptor (GPCR), expressed in immune cells and previously described as an entry co-factor for human and simian immunodeficiency viruses, is a crucial marker and homing receptor for a unique subset of intramucosal GPR15-guided regulatory CD8+ T lymphocytes (CD8+ TIGR). These cells potently kill macrophages that become aggressively activated in response to intestinal damage or disease. Thus, our identification of CD8+ TIGR cells yields new insights into organ-specific immune regulation and potential treatment strategies for IBD.

• Type: Exome Sequencing
• Archive: The database of Genotypes and Phenotypes (dbGaP)