Proenkephalin+ regulatory T cells expanded by ultraviolet-B exposure maintain skin homeostasis with a healing function
Ultraviolet B (UVB) is used as an effective therapy for individuals with psoriasis and atopic dermatitis because it has an immunosuppressive effect. The immune system develops to protect the body from infection or cancer. Its activation affects many physiological functions. Regulatory T (Treg) cells, expressing CD25 and Foxp3, constitute about 5-10% of peripheral CD4+T cells and work as brake on the immune system through the suppression of various immune responses. We previously showed that skin Treg cells were expanded by UVB up to about 60% of CD4+T cells. Here we found that UVB-expanded skin Treg (UVB-skin Treg) cells had a healing function. UVB-skin Treg cells expressed proenkephalin (PENK), an endogenous opioid precursor, and amphiregulin (AREG), the epidermal growth factor receptor ligand, which promoted wound healing in vivo and keratinocyte outgrowth in a skin explant assay. Our results provide a new implication in developing a novel therapy using PENK+UVB-skin Treg cells.
Proceedings of the National Academy of Sciences of the United States of America
Published online Date
Monday, August 3rd, 2020 3 PM US ET.
|Title||Proceedings of the National Academy of Sciences of the United States of America
|Author||Hiroaki Shime(a)(*), Mizuyu Odanaka(a)(*), Makoto Tsuiji(b),Takuma Matoba(a)(c),Masaki Imai(a), Yoshiaki Yasumizu(d), Ryuta Uraki(a), Kiyoshi Minohara(a)(c), Maiko Watanabe(a), Anthony John Bonito(e), Hidehiro Fukuyama(f), Naganari Ohkura(d)(g), Shimon Sakaguchi(d), Akimichi Morita(h), and Sayuri Yamazaki(a)(♯)
(a)Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
(b)Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Shinagawa-ku, Tokyo 142-8501, Japan.
(c)Department of Oto-rhino-laryngology and Head-and-neck-surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
(d)Department of Experimental Immunology, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
(e)Immunoassay Research & Development, Laboratory Diagnostics, Siemens Healthineers, Tarrytown, NY 10591, USA.
(f)Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
(g)Immunopharmaceutical Development Unit, Center of Medical Innovation Research, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
(h)Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
(*) Equally contribution.
(♯) Correspondence author