PD02 Molecular responses of human skin to single and repeated low-dose ultraviolet radiation exposure

Abstract

Ultraviolet radiation (UVR) is a major environmental factor affecting human skin, yet the early molecular effects of everyday low-dose exposure remain poorly understood. The objective of this study was to examine the acute molecular and cellular responses to low-dose single and repeated UVR exposure in healthy human skin. Six volunteers (five female, one male; age 28–65 years; skin types II–III) received 10 J cm−2 of solar simulated UVR (290–400 nm), equivalent to around 30 min of UK midday summer sunlight, on an area of upper buttock skin on three consecutive days. Skin biopsies were collected at 30 min, 3 h and 24 h after the first exposure, at 24 h following the third exposure, and from unexposed skin. Biopsies were analysed using immunohistochemistry and RNA sequencing, with predictive analysis from Ingenuity Pathway Analysis software. A single UVR exposure induced only modest transcriptional changes, with 27, 87 and 137 differentially expressed genes (> 1 log2 fold change, q < 0.05) detected at 30 min, 3 h and 24 h, respectively. In contrast, repeated daily exposure induced a pronounced response, with 1498 differentially expressed genes, including 333 long noncoding RNAs. Enriched pathways included cell cycle regulation, melanogenesis, interferon signalling and proinflammatory responses, with predicted activation of upstream regulators ELDR, MITF, VEGF genes, TNF and interferons. Immunohistochemistry after three exposures showed increased epidermal proliferation (Ki-67) and mild immune infiltration (CD4+ and CD8+ T cells, dendritic cells and neutrophils). CIBERSORT also suggested shifts in immune cell proportions after repeated UVR, although these changes were not statistically significant. These findings provide insights into the wide range of transcriptional changes occurring in healthy human skin following low-dose UVR exposure, and indicate that the skin does not return to baseline within 24 h, resulting in cumulative effects with subsequent exposures. Brief UVR exposures as experienced in daily life may profoundly influence skin physiology and health.