Interleukin 7 (IL-7) selectively promotes mouse and human IL-17–producing γδ cells

IL-17–producing CD27 ⁻ γδ cells (γδ ²⁷⁻ cells) are widely viewed as innate immune cells that make critical contributions to host protection and autoimmunity. However, factors that promote them over IFN-γ–producing γδ ²⁷⁺ cells are poorly elucidated. Moreover, although human IL-17–producing γδ cells are commonly implicated in inflammation, such cells themselves have proved difficult to isolate and characterize. Here, murine γδ ²⁷⁻ T cells and thymocytes are shown to be rapidly and substantially expanded by IL-7 in vitro and in vivo. This selectivity owes in substantial part to the capacity of IL-7 to activate STAT3 in such cells. Additionally, IL-7 promotes strong responses of IL-17–producing γδ cells to TCR agonists, thus reemphasizing the cells’ adaptive and innate potentials. Moreover, human IL-17–producing γδ cells are also substantially expanded by IL-7 plus TCR agonists. Hence, IL-7 has a conserved potential to preferentially regulate IL-17–producing γδ cells, with both biological and clinical implications.