Skin γδ T cell subsets have distinct functions in alopecia areata 3844

Abstract Description Alopecia areata is an autoimmune disease of the skin characterized by nonscarring, patchy hair loss across the scalp, affecting roughly 1.7% of the global population. Genetic susceptibility and environmental factors contribute to the onset of alopecia areata. Cytotoxic CD8+ T cells infiltrate the intrafollicular region of the hair follicle and degrade immune privilege in an IFN-dependent manner. Our lab has shown that γδ T cells are also increased in the epidermis of mice during alopecia areata, however less is known about their exact role in disease progression. Through reanalysis of publicly available single cell RNA sequencing data obtained from mouse and human skin, we have identified which genes are upregulated in γδ T cells in alopecia areata skin. Dermal Vγ6Vδ1 T cells upregulate IL17a similar to responses in psoriasis. Vγ4Vδ1 T cells upregulate genes associated with T cell recruitment and localization (CXCL10) suggesting a role in amplifying the Th1 response. Epidermal γδ T cells upregulate genes involved in inflammation including STAT1 and SCA-1/Ly6a. STAT1 regulates SCA-1/Ly6a expression and IFN responses. We validated the upregulation of STAT1 and Ly6a in skin γδ T cells from C3H/HeJ mice with alopecia areata using immunofluorescent microscopy. Our findings show direct involvement of γδ T cells in alopecia areata disease pathogenesis with distinct contributions by particular skin γδ T cell subtypes that are now being examined in human skin. Funding Sources Supported by Conrad Prebys Foundation; NIH T32GM146604; R15DK127440 Topic Categories Basic Autoimmunity (BA)