Dysregulated production of IL-17 by γδ T cells in the absence of interleukin-15 receptor α (59.2)

Abstract

Abstract Interleukin (IL)-15 and the IL-15 receptor α-chain (IL-15Rα) are required for the homeostasis of certain subsets of γδ T cells. We sought to determine if IL-15 signaling was also required for the generation and maintenance of a unique subset of IL-17-producing (IL-17+) γδ T cells. Surprisingly, we found a significant increase in the percentage and total number of IL-17+ γδ T cells in IL-15Rα KO (RKO) mice, most notably in the spleen, mesenteric lymph node, liver, and thymus. By generating mixed chimeras from WT and RKO neonatal thymocytes, we determined that the effect was not cell-intrinsic since WT- and RKO-derived γδ T cells exhibited equivalent IL-17 production. Considering the dissemination of IL-17+ γδ T cells to peripheral tissues, we hypothesized that their migration could be altered in RKO mice. Using parabiosis, we found that IL-17+ γδ T cells did not equally distribute between joined WT mice, suggesting limited recirculation, but also observed unexpected recirculation of IL-17+ γδ T cells into the thymus. When comparing WT:WT versus RKO:RKO parabionts, there was a significant increase in the percentage of IL-17+ cells in the donor γδ T cell population of RKO pairs, suggesting increased recirculation in the IL-15Rα-deficient environment. These findings support the presence of a cell-extrinsic effect of IL-15Rα signaling in regulating the IL-17+ γδ T cell subset. Further studies will continue to dissect the mechanism(s) by which this regulation occurs.