Reply to Slominski et al.: UVB irradiation induces proenkephalin+ regulatory T cells with a wound-healing function

(Treg) consti-tute about 10% of peripheral CD4 + T cells and sup-press a variety of immune responses in mice and humans (1). Our recent report (2) shows that proenkephalin (PENK)-expressing Treg cells expanded by ultraviolet B (UVB) exposure promoted wound healing. The Letter from Slominski et al. (3) points out that skin-resident cells produce enkephalins and other neuropeptides and that skin neuroendocrine activity exerted by keratinocytes, fibroblasts, and melanocytes was detected early after UVB irradiation within a day (3 – 6), although they did not address possible roles of PENK produced by skin T cells (3 – 6). In responding to their comments, we would like to emphasize that the focus of our study is to inves-tigate unique features of skin Treg cells that were expanded by UVB irradiation to about 60% of CD4 + T cells, with a peak of their expansion 7 d after irradiation (7, 8). By further advancing this finding, we have found that skin Treg cells expanded by UVB irradiation expressed PENK and also wound-healing – related genes including Areg encoding amphiregulin (AREG), a key tissue repair factor secreted by Treg cells (2). Moreover, we