Naoto Sasaki1, Tomoya Yamashita2, Kazuyuki Kasahara2, Atsushi Fukunaga2, Tomoyuki Yamaguchi2, Takuo Emoto2, Keiko Yodoi2, Takuya Matsumoto2, Kenji Nakajima2, Tomoyuki Kita2, Masafumi Takeda2, Taiji Mizoguchi2, Tomohiro Hayashi2, Yoshihiro Sasaki2, Mayumi Hatakeyama2, Kumiko Taguchi2, Ken Washio2, Shimon Sakaguchi2, Bernard Malissen2, Chikako Nishigori2, Ken-Ichi Hirata2. 1. From the Division of Cardiovascular Medicine, Department of Internal Medicine (N.S., T. Yamashita., K.K., T.E., K.Y., T. Matsumoto, K.N., T.K., M.T., T. Mizoguchi, T.H., Y.S., K.-i.H.) and Division of Dermatology, Department of Internal Related (A.F., M.H., K.T., K.W., C.N.), Kobe University Graduate School of Medicine, Japan; Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Japan (N.S.); Department of Single Molecule Imaging (T. Yamaguchi) and Department of Experimental Immunology (S.S.), World Premier International Immunology Frontier Research Center, Osaka University, Japan; Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan (M.T.); and Centre d'Immunologie de Marseille-Luminy and the Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France (B.M.). n-sasaki@kobepharma-u.ac.jp tomoya@med.kobe-u.ac.jp. 2. From the Division of Cardiovascular Medicine, Department of Internal Medicine (N.S., T. Yamashita., K.K., T.E., K.Y., T. Matsumoto, K.N., T.K., M.T., T. Mizoguchi, T.H., Y.S., K.-i.H.) and Division of Dermatology, Department of Internal Related (A.F., M.H., K.T., K.W., C.N.), Kobe University Graduate School of Medicine, Japan; Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Japan (N.S.); Department of Single Molecule Imaging (T. Yamaguchi) and Department of Experimental Immunology (S.S.), World Premier International Immunology Frontier Research Center, Osaka University, Japan; Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan (M.T.); and Centre d'Immunologie de Marseille-Luminy and the Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France (B.M.).
Abstract
OBJECTIVE: UVB irradiation is an established treatment for immunoinflammatory cutaneous disorders and has been shown to suppress cutaneous and systemic inflammatory diseases through modulation of the adaptive immune response. However, it remains unknown whether UVB irradiation prevents an immunoinflammatory disease of arteries such as atherosclerosis. APPROACH AND RESULTS: Here, we show that UVB exposure inhibits the development and progression of atherosclerosis in atherosclerosis-prone mice by expanding and enhancing the functional capacity of CD4+ forkhead box P3+ regulatory T cells and regulating proatherogenic T-cell responses. Experimental studies in Langerhans cell-depleted mice revealed that epidermal Langerhans cells play a critical role in UVB-dependent induction of CD4+ forkhead box P3+ regulatory T cells, suppression of proatherogenic T-cell responses, and prevention of atherosclerotic plaque development. CONCLUSIONS: Our findings suggest the skin immune system as a novel therapeutic target for atherosclerosis and provide a novel strategy for the treatment and prevention of atherosclerosis.
OBJECTIVE: UVB irradiation is an established treatment for immunoinflammatory cutaneous disorders and has been shown to suppress cutaneous and systemic inflammatory diseases through modulation of the adaptive immune response. However, it remains unknown whether UVB irradiation prevents an immunoinflammatory disease of arteries such as atherosclerosis. APPROACH AND RESULTS: Here, we show that UVB exposure inhibits the development and progression of atherosclerosis in atherosclerosis-prone mice by expanding and enhancing the functional capacity of CD4+ forkhead box P3+ regulatory T cells and regulating proatherogenic T-cell responses. Experimental studies in Langerhans cell-depleted mice revealed that epidermal Langerhans cells play a critical role in UVB-dependent induction of CD4+ forkhead box P3+ regulatory T cells, suppression of proatherogenic T-cell responses, and prevention of atherosclerotic plaque development. CONCLUSIONS: Our findings suggest the skin immune system as a novel therapeutic target for atherosclerosis and provide a novel strategy for the treatment and prevention of atherosclerosis.
Authors: A F Bais; R M Lucas; J F Bornman; C E Williamson; B Sulzberger; A T Austin; S R Wilson; A L Andrady; G Bernhard; R L McKenzie; P J Aucamp; S Madronich; R E Neale; S Yazar; A R Young; F R de Gruijl; M Norval; Y Takizawa; P W Barnes; T M Robson; S A Robinson; C L Ballaré; S D Flint; P J Neale; S Hylander; K C Rose; S-Å Wängberg; D-P Häder; R C Worrest; R G Zepp; N D Paul; R M Cory; K R Solomon; J Longstreth; K K Pandey; H H Redhwi; A Torikai; A M Heikkilä Journal: Photochem Photobiol Sci Date: 2018-02-14 Impact factor: 3.982
Authors: Hong S Lu; Ann Marie Schmidt; Robert A Hegele; Nigel Mackman; Daniel J Rader; Christian Weber; Alan Daugherty Journal: Arterioscler Thromb Vasc Biol Date: 2018-10 Impact factor: 8.311