γδ T cells coexpressing gut homing α4β7 and αe integrins define a novel subset promoting intestinal inflammation

γδ T lymphocytes, dominant T cell subsets in the intestine, mediate both regulatory and pathogenic roles, yet the mechanisms underlying such opposing effects remain unclear. In this study, we identified a unique gd T cell subset that coexpresses high levels of gut-homing integrins, CD103 and a4b7. They were exclusively found in the mesenteric lymph node after T cell-mediated colitis induction, and their appearance preceded the inflammation. Adoptive transfer of the CD103+a4b7high subsets enhanced Th1/Th17 T cell generation and accumulation in the intestine, and the disease severity. The level of generation correlated with the disease severity. Moreover, these cells were also found to be elevated in a spontaneous mouse model of ileitis. Based on the procolitogenic function, we referred to this subset as "inflammatory" gd T cells. Targeting inflammatory gd T cells may open a novel strategy to treat inflammatory diseases where gd T cells play a pathogenic role including inflammatory bowel disease.