Abstract The hair follicle is a site of immune privilege that, when disrupted, results in the autoimmune disorder alopecia areata. 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. 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 resting epidermal γδ T cells express MC1R, and TCR stimulation increases MC1R expression. Upregulation of MC1R expression is augmented further by stimulation with α-MSH. Epidermal γδ T cells significantly upregulate immunostimulatory cytokines when stimulated with anti-CD3, but cytokine production did not significantly change with the addition of α-MSH. Additional findings suggest that α-MSH instead plays a role in MC1R regulated pathways such as DNA repair and cell survival. 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.