Gene profiling of narrow-band UVB-induced skin injury defines cellular and molecular innate immune responses

The acute response of human skin to ultraviolet B (UVB) radiation has not been fully characterized. We sought to define the cutaneous response at 24 hours following narrow-band UVB (NB-UVB, 312 nm peak), a therapeutically relevant source of UVB, using transcriptional profiling, immunohistochemistry, and immunofluorescence. There were 1,522 unique differentially-regulated genes, including upregulation of antimicrobial peptides (AMPs) (S100A7, S100A12, human beta-defensin 2, and elafin), neutrophil and monocyte/dendritic cell (DC) chemoattractants (IL-8, CXCL1, CCL20, CCL2). Ingenuity Pathway Analysis demonstrated activation of innate defense and early adaptive immune pathways. Immunohistochemistry confirmed increased epidermal staining for AMPs (S100A7, S100A12, human beta-defensin 2, and elafin). Inflammatory myeloid CD11c + BDCA1 − DCs were increased in irradiated skin, which were immature as shown by minimal co-localization with DC-LAMP, and co-expressed inflammatory markers TNF and TRAIL in irradiated skin. There were increased BDCA3 + DCs, a cross-presenting DC subtype with immunosuppressive functions, and these cells have not been previously characterized as part of the response to UVB. These results show that the acute response of human skin to erythemogenic doses of NB-UVB includes activation of innate defense mechanisms, as well as early infiltration of multiple subtypes of inflammatory DCs, which could serve as a link between innate and adaptive immunity.

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