title: UVB Exposure Prevents Atherosclerosis by Regulating Immunoinflammatory Responses.
abstract: 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.
  
  
  
  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.
  
  
  
  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.affiliation: 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.
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: 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.).
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: 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.).
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kasahara
authors.affiliation: 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.).
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukunaga
authors.affiliation: 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.).
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: 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.).
authors.forename: Takuo
authors.initials: T
authors.lastname: Emoto
authors.affiliation: 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.).
authors.forename: Keiko
authors.initials: K
authors.lastname: Yodoi
authors.affiliation: 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.).
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: 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.).
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: 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.).
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kita
authors.affiliation: 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.).
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.affiliation: 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.).
authors.forename: Taiji
authors.initials: T
authors.lastname: Mizoguchi
authors.affiliation: 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.).
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: 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.).
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: 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.).
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hatakeyama
authors.affiliation: 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.).
authors.forename: Kumiko
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: 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.).
authors.forename: Ken
authors.initials: K
authors.lastname: Washio
authors.affiliation: 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.).
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.affiliation: 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.).
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.affiliation: 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.).
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
authors.affiliation: 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.).
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D001018:Aortic Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D008213:Lymphocyte Activation / Q000528:radiation effects; D018345:Mice, Knockout; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D015398:Signal Transduction / Q000528:radiation effects; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D001057:Apolipoproteins E; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse
keywords: atherosclerosis; immunology; inflammation; lymphocytes; ultraviolet rays