GPR15 directs gut-homing CD8+ regulatory T cells to dampen intestinal inflammation

Researchers identify GPR15 as a marker and homing receptor for a mucosal subset of CD8+ regulatory T cells (CD8+ TIGR) that suppress intestinal inflammation. In humans, GPR15 variants that impair this homing are linked to severe early-onset IBD, and CD8+ TIGR are reduced in sporadic IBD. In mice, GPR15 deficiency hampers colonic homing of these cells, leading to inflammatory macrophage accumulation; CD8+ TIGR can kill activated macrophages via FasL and TWEAK, highlighting a potential new immunotherapeutic avenue for IBD.