Skin regulatory T cells possessing a healing function are expanded by ultraviolet-B exposure

Tissue-specific physiological functions of regulatory T (Treg) cells are critical for the maintenance of tissue homeostasis. Here, we demonstrate that skin Treg cells possessing a healing function are expanded by ultraviolet-B (UVB) exposure. Compared to Treg cells in muscle, visceral adipose tissue and brain, the UVB-expanded skin Treg (UVB-skin Treg) cells highly expressed a distinctive set of genes enriched in wound healing involved in inflammatory responses and neuropeptide signaling pathway such as Penk, which encodes proenkephalin (PENK). Upon UVB irradiation, Treg cells showed an activated phenotype with the expression of PENK and Amphlegrin (AREG) at the protein level. Single cell TCR repertoire analysis showed UVB-skin Treg cells had a clonal expansion. Moreover, UVB-skin Treg cells suppressed UVB-induced inflammation and promoted wound healing in both, an in vivo assay and ex vivo skin explant assay. These results showed that UVB exposure expands skin Treg cells with a healing function, which is beneficial to maintain skin homeostasis.