Role of Distinct Fibroblast Lineages and Immune Cells in Dermal Repair Following UV Radiation Induced Tissue Damage

June 2021 in “ bioRxiv (Cold Spring Harbor Laboratory) ”

Emanuel Rognoni, Georgina Goss, Toru Hiratsuka, Katharina I Kober, Prudence PokWai Lui, Victoria Tsang, Nathan J. Hawkshaw, Suzanne M. Pilkington, Kalle Sipilä, Inchul Cho, Niwa Ali, Lesley E. Rhodes, Fiona M. Watt

UV radiation fibroblasts immune cells papillary fibroblasts Wnt-signalling β-catenin neutrophils T cells CD4 cells CD8 cells COX-2 inhibition pro-inflammatory signalling DNA damage UVR COX-2 inhibitors

Studysummary This study found that fibroblast loss in the upper dermis from UVR exposure is linked to a deregulated inflammatory response, with T cells playing a protective role in fibroblast survival.

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The study investigated the role of fibroblast lineages and immune cells in dermal repair following UV radiation-induced damage. It was found that acute and chronic UVR exposure led to a selective loss of fibroblasts in the upper dermis. Papillary fibroblast proliferation and migration were key in repairing acute UVR damage, while chronic exposure resulted in permanent fibroblast loss. The study highlighted that UVR activated Wnt-signalling, but epidermal β-catenin stabilisation did not aid in dermis repair. Acute UVR increased neutrophil and T cell infiltration, with CD4 and CD8 cell depletion exacerbating fibroblast loss and DNA damage. Topical COX-2 inhibition was effective in preventing fibroblast depletion and neutrophil infiltration. The findings suggested that fibroblast loss was primarily due to a deregulated inflammatory response, with T cells playing a supportive role in fibroblast survival under UVR stress.

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