Th1 and Th17 cells are often colocalized in autoimmune environments such as psoriasis and multiple sclerosis. It has been proposed that Th1 and Th17 cells collaboratively contribute to human autoimmune diseases. In a psoriasis study, IFN-c has been shown to be a potent promoter of IL-17+ T cell trafficking, induction and function in Z-VAD-FMK humans. In a mouse model, adoptively transferred Th17 polarized cells were able to mediate destruction of advanced B16 melanoma and induce vitiligo, but this therapeutic effect was critically dependent on IFNc production, whereas IL-17A and IL-23 depletion had little impact. Our study shows that in leading edge vitiligo biopsies, there is an active Th17 component in addition to a Th1 component. The interplay between Th1 and Th17 populations in vitiligo remains an intriguing avenue for future exploration. Interleukin 17 can be produced by both CD4+ and CD8+ T cells, as well as natural killer cells and natural killer T cells. In this study, we could not obtain shave biopsies from vitiligo patients to phenotype IL-17A producing T cells by FACS, but we do observe IL17A+ T cells in the dermal area of leading edge vitiligo biopsies, as well as CD8+ cells infiltrating the basal layer of the epidermis. We also see significant colocalization of IL-17A and IL- 17 receptor A in leading edge vitiligo skin. It has been reported that vitiligo patients possess high Vismodegib frequencies of circulating CD8+ T lymphocytes specific for Melan-A, and melanoma patients who went through Melan-A specific CD8+ T cell infusion immunotherapy demonstrated melanocyte loss in regions of normal skin. IL-1? is a key cytokine for the development of Th17 cells, and it is activated in the inflammasomes formed by NOD-like receptors . NALP1 is widely expressed at low levels, but is present at a high level in immune cells, particularly T cells and Langerhans cells, which may explain the high IL-1? levels in leading edge vitiligo biopsies. One of the consequences of cytokine-orchestrated inflammation is apoptosis. In addition to CD8+ cytotoxic T cell-mediated killing, melanocyte loss in the leading edge of vitiligo skin may result in part from increased synthesis and release of IL-1?, and the accompanying apoptotic microenvironment at the dermal-epidermal junctions. Th17 cells are antigen restricted, and therefore the development of autoimmune T cells would require antigen presentation by dendritic cells. In theory, both Langerhans cells and dermal dendritic cells could present antigens to T cells. Langerhans cells appeared to be activated in leading edge and depigmented skin based on their high HLA-DR expression and their location in the epidermis could lead to direct contact with melanocyte processes or cellular antigens. Alternatively, inflammatory CD11c+ DCs that invade the epidermis might also capture melanocyte antigens. As already recognized, inflammatory dermal dendritic cells may stimulate Th17 cell proliferation through their production of IL-23.