Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation induced tissue damage

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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin. Lineage tracing and in vivo live imaging revealed that repair following acute UVR is predominantly mediated by papillary fibroblast proliferation and fibroblast reorganisation occurs with minimal migration. In contrast, chronic UVR exposure led to a permanent loss of papillary fibroblasts, with expansion of fibroblast membrane protrusions partially compensating for the reduction in cell number. Although UVR strongly activated Wnt-signalling in skin, stimulation of fibroblast proliferation by epidermal b-catenin stabilisation did not enhance papillary dermis repair. Acute UVR triggered an infiltrate of neutrophils and T cell subpopulations and increased pro-inflammatory prostaglandin signalling in skin. Depletion of CD4 and CD8 positive cells resulted in increased papillary fibroblast depletion, which correlated with an increase in DNA damage, pro-inflammatory prostaglandins and reduction in fibroblast proliferation. Conversely, topical COX-2 inhibition prevented fibroblast depletion and neutrophil infiltration after UVR. We conclude that loss of papillary fibroblasts is primarily induced by a deregulated inflammatory response, with infiltrating T cells supporting fibroblast survival upon UVR-induced environmental stress.

Original languageEnglish
Article numbere71052
JournaleLife
Volume10
Early online date23 Dec 2021
DOIs
Publication statusPublished - Dec 2021

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