Chronic UV exposure decreases sun sensitivity by a tanning independent mechanism

Abstract

Keratinocytes protect themselves from UV-induced damage and death by signalling to melanocytes to produce and transfer melanin to protect their nuclei from further UV damage. The keratinocyte-melanocyte communication axis defines the tanning response, which is integral to epidermal homeostasis. We studied the effects of occasional, moderate and chronic UVA/UVB exposure on keratinocytes in vitro using immortalised human keratinocytes in monoculture. We show that UV exposure led to UV signature 7 mutations with predominant C>T nucleotide substitutions across the genome. We observed that keratinocytes with any UV treatment history were better able to withstand further UV exposure, showing decreased UV sensitivity, despite the absence of melanin transfer from melanocytes. We explored our findings in vivo using immunocompetent wild type mice, and observed a striking decrease in sunburn cells (apoptotic keratinocytes), TUNEL, p53 and TT-dimers 24 hours after UV exposure in skin that had a prior history of significant UV damage. This in vivo response is independent of melanin protection, as mouse melanocytes are intradermal and do not transfer melanin to epidermal keratinocytes. These data show that chronic UV confers protection to further UV exposure independently of the tanning response. We are investigating transcriptional and immune changes that may infer a mechanism.