Proenkephalin <sup>+</sup> regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function
Hiroaki Shime, Mizuyu Odanaka, Makoto Tsuiji, Takuma Matoba, Masaki Imai, Yoshiaki Yasumizu, Ryuta Uraki, Kiyoshi Minohara, Maiko Watanabe, Anthony Bonito, Hidehiro Fukuyama, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita, Sayuri Yamazaki
Abstract
Significance Regulatory T (Treg) cells, expressing CD25 and Foxp3, constitute about 5 to 10% of peripheral CD4 + T cells and maintain immunological self-tolerance through the suppression of various immune responses. Here we found that skin Treg cells expanded by UVB exposure possess a unique TCR repertoire and a healing function. UVB-expanded skin Treg (UVB-skin Treg) cells expressed proenkephalin (PENK), an endogenous opioid precursor, and amphiregulin (AREG), the epidermal growth factor receptor ligand. The Treg-derived PENK and AREG promoted keratinocyte outgrowth in a skin explant assay. Moreover, UVB-expanded skin Treg cells played a key role in promoting wound healing in vivo. Our results provide a new implication in developing a therapy using PENK + UVB-skin Treg cells.