Proenkephalin(+) regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function
| Autor: | Anthony J. Bonito, Hidehiro Fukuyama, Naganari Ohkura, Ryuta Uraki, Yoshiaki Yasumizu, Maiko Watanabe, Shimon Sakaguchi, Takuma Matoba, Masaki Imai, Akimichi Morita, Mizuyu Odanaka, Makoto Tsuiji, Hiroaki Shime, Sayuri Yamazaki, Kiyoshi Minohara |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Multidisciplinary integumentary system Chemistry FOXP3 hemic and immune systems chemical and pharmacologic phenomena Biological Sciences Proenkephalin Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system Amphiregulin 030220 oncology & carcinogenesis IL-2 receptor Neuropeptide signaling pathway Wound healing skin and connective tissue diseases Endogenous opioid |
| Zdroj: | Proc Natl Acad Sci U S A |
| Popis: | Regulatory T (Treg) cells, expressing CD25 (interleukin-2 receptor α chain) and Foxp3 transcription factor, maintain immunological self-tolerance and suppress various immune responses. Here we report a feature of skin Treg cells expanded by ultraviolet B (UVB) exposure. We found that skin Treg cells possessing a healing function are expanded by UVB exposure with the expression of an endogenous opioid precursor, proenkephalin (PENK). Upon UVB exposure, skin Treg cells were expanded with a unique TCR repertoire. Also, they highly expressed a distinctive set of genes enriched in “wound healing involved in inflammatory responses” and the “neuropeptide signaling pathway,” as indicated by the high expression of Penk. We found that not only was PENK expression at the protein level detected in the UVB-expanded skin Treg (UVB-skin Treg) cells, but that a PENK-derived neuropeptide, methionine enkephalin (Met-ENK), from Treg cells promoted the outgrowth of epidermal keratinocytes in an ex vivo skin explant assay. Notably, UVB-skin Treg cells also promoted wound healing in an in vivo wound closure assay. In addition, UVB-skin Treg cells produced amphiregulin (AREG), which plays a key role in Treg-mediated tissue repair. Identification of a unique function of PENK(+) UVB-skin Treg cells provides a mechanism for maintaining skin homeostasis. |
| Databáze: | OpenAIRE |
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