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.

based on the known additive or synergistic activity of AMP (23), it is likely that lactoferrin works together with the other AMP at the skin surface to provide an immune defense. Supporting InformationAdditional Supporting Information may be found in the online version of this article: Data S1. Functional classification of sweat proteins. Table S1. Proteome list from sweat by LC-MS ⁄ MS. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Tobacco smoke is related to Th17 generation with clinical implications for psoriasis patientsKan Torii, Chiyo Saito, Takuya Furuhashi, Akiko Nishioka, Yoichi Shintani, Kana Kawashima, Hiroshi Kato and Akimichi Morita Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Correspondence: Kan Torii, Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan, Tel.: +81-52-853-8261, Fax: +81-52-852-5449, e-mail: kan042033@live.jp Abstract: Environmental factors contribute to the increased prevalence of autoimmune diseases via T helper type-17 cell (Th17) activation. Tobacco smoking increases the risk of psoriasis, but the mechanisms are not clear. We evaluated the percentage of circulating Th17 among CD3 + cells in peripheral blood mononuclear cells (PBMC) obtained from 27 healthy volunteers (2.58 ± 0.80%), 33 smoker (3.55 ± 1.33%) and 21 non-smoker (3.10 ± 1.14%) patients with psoriasis to elucidate the relation between smoking and psoriasis. More smokers (19 ⁄ 33) than non-smokers (6 ⁄ 21) had high Th17 levels (Th17 ⁄ CD3 > 3.38%, mean + 1 SD of healthy volunteers). Tobacco smoke extract (TSE, 7 ll ⁄ ml) induced Th17 generation from central memory T cells in vitro. TSE increased interleukin 17 and 22 expression. These findings demonstrate the relation between tobacco smoke and IL-17 and IL-22, which exacerbate psoriasis.

Skin dendritic cells (DCs) are divided into several subsets with distinctive functions. This study shows a previously unappreciated role of dermal CD11b-type Langerin DCs in maintaining immunological self-tolerance after UVB exposure. After UVB exposure, dermal CD11b-type Langerin DCs upregulated surface CD86 expression, induced proliferation of Foxp3 regulatory T (Treg) cells without exogenous Ags, and upregulated a set of genes associated with immunological tolerance. This Treg-expansion activity was significantly hampered by CD80/CD86 blockade in vivo. These results indicate that CD11b-type Langerin DCs from the UVB-exposed skin are specialized to expand Treg cells in the skin, which suppress autoimmunity.

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Background: Photosensitizers used for photodynamic therapy (PDT) to treat dermatologic disease are metabolized into mainly protoporphyrin IX (PpIX), which has five absorption wavelength peaks: 410 nm, 510 nm, 545 nm, 580 nm, and 630 nm. Although only red light around 635 nm and blue light around 400 nm are used as light sources for PDT, the efficiency of PDT might be improved by using multiple wavelengths, including those that correspond to the other absorption peaks of PpIX. Furthermore, because the target disease often occurs on the face, a flexible-type light-source unit that can be fitted to the lesion without unnecessarily exposing the mucous membranes, e.g., the eyes, nostrils, and mouth, is preferred. Objective: We investigated the efficacy of a flexible light-emitting diode (LED) unit that emits multiple wavelengths to improve PDT effects. Methods: HaCaT cells were incubated with 5-ALA and subsequently irradiated with either a single wavelength or sequentially with two wavelengths. Cell viability and reactive oxygen species were analyzed. Nude mice were implanted with COLO679 cells by subcutaneous injection into the flank. 5-ALA was subcutaneously injected into the tumor. The tumor was irradiated with 50 J/cm 2 (day 0) and assessed daily until day 21. Results: The synergistic PDT effects of dual-wavelength irradiation and reactive oxygen species production were highest with the 405-nm and 505-nm wavelength combination. This dual wavelength combination was also the most effective in vivo. Conclusion: We could therefore conclude that dual-wavelength PDT is an efficient strategy for improving the therapeutic effects of PDT. Using a flexible LED unit is expected to achieve more uniform irradiation of uneven areas.