Long-Lived Innate IL-17-Producing γ/δ T Cells Modulate Antimicrobial Epithelial Host Defense in the Colon

Intestinal IL-17-producing cells, including Th17, gamma/delta T, and innate lymphoid cells, are differentially distributed along the gastrointestinal tract. In this study, we show that the gut IL-17-producing gamma/delta T (gamma/delta T17) cells develop before birth and persist in the tissue as long-lived cells with minimal turnover. Most colon g/d T17 cells express, together with V gamma 4 and CCR6, the scavenger receptor 2 and are mainly restricted to innate lymphoid follicles in the colon. Colon gamma/delta T cells in mice that lack conventional dendritic cells 2 produced increased amounts of IL-17 with concomitant heightened epithelial antimicrobial response, such as the C-type lectins Reg3 gamma and Reg3 beta. In the absence of gamma/delta T cells or after IL-17 neutralization, this epithelial response was dramatically reduced, underlining the protective role of this unique subpopulation of innate gamma/delta T17 cells in the colonic mucosa.