Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6 IL-17-producing γδ T cells (IRC8P.479)

Abstract

Abstract Dermal γδ T cells are professional IL-17-producing γδ T cells and play a critical role in skin inflammation. However, their development and peripheral regulation are still largely unknown. In this study, we demonstrated that dermal γδ T cells developed from fetal thymus and underwent homeostatic proliferation after birth with diversified TCR repertoire, mainly including Vγ4 and Vγ6. Thymus is absolutely required for dermal γδ T cell development. IL-17-producing Vγ6 T cells were bona fide resident in dermis and were reconstituted from fetal thymus while IL-17-producing Vγ4 dermal γδ T cells were mainly from bone marrow, suggesting precursors of dermal Vγ4 T cells may require extrathymic environment for maturation and gaining skin-homing property. In addition, we found that Vγ6 T cells were pathogenic to induce skin inflammation. Mice reconstituted with Vγ6 developed psoriasis-like skin inflammation upon IMQ application whereas Vγ4 T cells were preferentially expanded and the major IL-17 producer in IMQ-treated naïve mice. Although IL-23 and IL-1β were capable of driving dermal Vγ4 and Vγ6 T cell proliferation, IL-17 production was mainly from Vγ4 and IL-1 signaling was essential. These studies reveal a differential developmental requirement and peripheral regulation for IL-17-producing dermal Vγ6 and Vγ4 T cells. This work is supported by a grant from the National Psoriasis Foundation.