title: Homeostasis of thymus-derived Foxp3+ regulatory T cells is controlled by ultraviolet B exposure in the skin.
abstract: Accumulating evidence shows that immunological tolerance induced by Ag administration together with UVB irradiation is dependent on Foxp3(+) CD4(+) regulatory T (Treg) cells. However, the mechanisms by which UVB controls Treg cells in the skin are currently unclear. In this study, we have shown that exposure to UVB induced expansion of Treg cells up to 50-60% of the CD4(+) T cells in the irradiated skin. The Treg cell expansion in the skin lasted for 2 wk after exposure, which contributed to homeostasis of Treg cells in the periphery later. UVB-expanded Treg cells formed clusters with dendritic cells and proliferated in situ. Furthermore, the expanded Treg cells appeared to derive from neuropilin 1(+) thymus-derived Treg (tTreg) cells in the periphery because UVB-expanded Treg cells possessed Treg cell-specific CpG hypomethylation pattern, as seen in tTreg cells. These results collectively indicate that homeostasis of tTreg cells is controlled by UVB exposure in the skin. UVB therapy may be useful for not only inflammatory skin disorders, but also autoimmunity, transplantation, and allergy.
authors.affiliation: Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; yamazas@med.nagoya-cu.ac.jp.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Yamazaki
authors.affiliation: Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan;
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishioka
authors.affiliation: Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan;
authors.forename: Saori
authors.initials: S
authors.lastname: Kasuya
authors.affiliation: Department of Experimental Immunology, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
authors.forename: Naganari
authors.initials: N
authors.lastname: Ohkura
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hemmi
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan; and.
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
authors.affiliation: Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Ophthalmology, Kochi Medical School, Nankoku 783-8505, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
authors.affiliation: Department of Experimental Immunology, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.affiliation: Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan;
authors.forename: Akimichi
authors.initials: A
authors.lastname: Morita
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D019175:DNA Methylation; D003713:Dendritic Cells / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006706:Homeostasis; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D039942:Neuropilin-1 / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014466:Ultraviolet Rays
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039942:Neuropilin-1