Exposure to ultraviolet radiation (UVR) is a major risk factor for skin cancers and skin inflammation. However, molecular and cellular mechanisms to minimize UV damage in the skin are incompletely understood. Based on their sentinel function, we hypothesized that resident T cells in the skin, murine dendritic epidermal T cells (DETC) and human skin-resident T cells, sense UVR-induced danger signals such as extracellular adenosine triphosphate (ATP) to initiate protection and repair. Supporting this hypothesis, we find that epidermal keratinocytes release ATP upon UVR to activate DETC and human skin-resident T cells in a direct and IL-1β-mediated manner and this response could be inhibited by ATPases. Using mice deficient in DETC, we show a previously unrecognized role for DETC in repairing keratinocyte DNA damage upon UVR. Functionally, ATP enhanced TCR-mediated DETC proliferation and IL-17A production. IL-17A induced molecules relevant to DNA repair and apoptosis in keratinocytes, including TNF related weak inducer of apoptosis (TWEAK) and Growth arrest and DNA damage gene (GADD45), providing a possible link to the observed UV protective mechanisms exerted by DETC. Ongoing studies quantifying UVR-induced DNA damage and apoptosis in wildtype, TCRδ-/-, and IL-17A-/- skin cells and in human skin cultures will provide novel information on skin-resident T cell function, and may identify new targets to treat and prevent sunburn and skin cancer in humans.
- Copyright © 2013 by The American Association of Immunologists, Inc.