title: Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair.
abstract: Skin-resident T cells have been shown to play important roles in tissue homeostasis and wound repair, but their role in UV radiation (UVR)-mediated skin injury and subsequent tissue regeneration is less clear. In this study, we demonstrate that acute UVR rapidly activates skin-resident T cells in humans and dendritic epidermal γδ T cells (DETCs) in mice through mechanisms involving the release of ATP from keratinocytes. Following UVR, extracellular ATP leads to an increase in CD69 expression, proliferation, and IL-17 production, and to changes in DETC morphology. Furthermore, we find that the purinergic receptor P2X7 and caspase-1 are necessary for UVR-induced IL-1 production in keratinocytes, which increases IL-17 secretion by DETCs. IL-17, in turn, induces epidermal TNF-related weak inducer of apoptosis and growth arrest and DNA damage-associated gene 45, two molecules linked to the DNA repair response. Finally, we demonstrate that DETCs and human skin-resident T cells limit DNA damage in keratinocytes. Taken together, our findings establish a novel role for skin-resident T cells in the UVR-associated DNA repair response and underscore the importance of skin-resident T cells to overall skin regeneration.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Amanda S
authors.initials: AS
authors.lastname: MacLeod
authors.affiliation: Division of Plastic Surgery, Scripps Clinic Torrey Pines, La Jolla, CA 92037; Division of Plastic Surgery, University of California San Diego, La Jolla, CA 92037; and.
authors.forename: Ross
authors.initials: R
authors.lastname: Rudolph
authors.affiliation: Division of Pharmacology and Drug Discovery, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093.
authors.forename: Ross
authors.initials: R
authors.lastname: Corriden
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Ivan
authors.initials: I
authors.lastname: Ye
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Olivia
authors.initials: O
authors.lastname: Garijo
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037; havran@scripps.edu.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Havran
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D004260:DNA Repair / Q000235:genetics / Q000276:immunology / Q000528:radiation effects*; D004817:Epidermis / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012038:Regeneration / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D020381:Interleukin-17; D037181:Lectins, C-Type; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens