The effects of alpha-MSH on dendritic epidermal T cell activation and function

The hair follicle is a site of immune privilege that, when disrupted, results in the autoimmune disorder alopecia areata (1). Although there are a variety of cell types that reside near the hair follicle and may be involved in the initiation of alopecia areata, few studies have focused on γδ T cells. γδ T cells are resident in epithelial tissues where they normally play roles in inflammation and wound healing. Alpha-melanocyte-stimulating(α-MSH) is an immunoregulator locally produced within the hair follicle. α-MSH ensures the immune system is suppressed during anagen phase (growth phase) and restored during catagen phase (resting phase). The effects of α-MSH on epidermal γδ T cells via MC1R, one of five melanocortin receptors, is unknown. We therefore purified primary epidermal γδ T cells to investigate the immunomodulatory effects of α-MSH on γδ T cells. Flow cytometry and the Luminex platform were used to compare changes in MC1R expression levels and cytokine production in response to α-MSH. Here we show that epidermal γδ T cell activation and function are not suppressed by α-MSH indicating MC1R may play a more primary role in γδ T cell survival and DNA repair. Epidermal γδ T cells upregulate immunostimulatory cytokines TNF-α and IP-10 when stimulated with α-MSH. Increased levels of IP-10 are consistent with acute phase alopecia areata onset suggesting α-MSH may play a role in DETC mediated progression of alopecia areata symptoms. This study begins to delineate the mechanisms by which α-MSH impacts γδ T cell function and leads to the disruption of immune privilege that occurs in alopecia areata.