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Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome.
Takemura, Naoki; Kawasaki, Takumi; Kunisawa, Jun; Sato, Shintaro; Lamichhane, Aayam; Kobiyama, Kouji; Aoshi, Taiki; Ito, Junichi; Mizuguchi, Kenji; Karuppuchamy, Thangaraj; Matsunaga, Kouta; Miyatake, Shoichiro; Mori, Nobuko; Tsujimura, Tohru; Satoh, Takashi; Kumagai, Yutaro; Kawai, Taro; Standley, Daron M; Ishii, Ken J; Kiyono, Hiroshi; Akira, Shizuo; Uematsu, Satoshi.
Afiliação
  • Takemura N; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
  • Kawasaki T; 1] Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [2] Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [3] Laboratory of Molecular
  • Kunisawa J; 1] Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan [2] Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, Ibaraki, Osak
  • Sato S; 1] Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan [2] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5 Sanbancho, Chiyod
  • Lamichhane A; Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
  • Kobiyama K; 1] Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, Ibaraki, Osaka 567-0085, Japan [2] Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Aoshi T; 1] Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, Ibaraki, Osaka 567-0085, Japan [2] Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Ito J; Laboratory of Bioinformatics, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, Ibaraki, Osaka 567-0085, Japan.
  • Mizuguchi K; Laboratory of Bioinformatics, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, Ibaraki, Osaka 567-0085, Japan.
  • Karuppuchamy T; 1] Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [2] Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Matsunaga K; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
  • Miyatake S; Laboratory of Self Defense Gene Regulation, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
  • Mori N; Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan.
  • Tsujimura T; Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
  • Satoh T; 1] Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [2] Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Kumagai Y; 1] Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [2] Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Kawai T; Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
  • Standley DM; Laboratory of Systems Immunology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Ishii KJ; 1] Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, Ibaraki, Osaka 567-0085, Japan [2] Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Kiyono H; 1] Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan [2] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5 Sanbancho, Chiyod
  • Akira S; 1] Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [2] Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Uematsu S; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nat Commun ; 5: 3492, 2014 Mar 18.
Article em En | MEDLINE | ID: mdl-24637670
ABSTRACT
High-dose ionizing radiation induces severe DNA damage in the epithelial stem cells in small intestinal crypts and causes gastrointestinal syndrome (GIS). Although the tumour suppressor p53 is a primary factor inducing death of crypt cells with DNA damage, its essential role in maintaining genome stability means inhibiting p53 to prevent GIS is not a viable strategy. Here we show that the innate immune receptor Toll-like receptor 3 (TLR3) is critical for the pathogenesis of GIS. Tlr3(-/-) mice show substantial resistance to GIS owing to significantly reduced radiation-induced crypt cell death. Despite showing reduced crypt cell death, p53-dependent crypt cell death is not impaired in Tlr3(-/-) mice. p53-dependent crypt cell death causes leakage of cellular RNA, which induces extensive cell death via TLR3. An inhibitor of TLR3-RNA binding ameliorates GIS by reducing crypt cell death. Thus, we propose blocking TLR3 activation as a novel approach to treat GIS.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND / 4_TD Base de dados: MEDLINE Assunto principal: Lesões por Radiação / Receptor 3 Toll-Like / Gastroenteropatias Limite: Animals / Female / Humans Idioma: En Revista: Nat Commun Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND / 4_TD Base de dados: MEDLINE Assunto principal: Lesões por Radiação / Receptor 3 Toll-Like / Gastroenteropatias Limite: Animals / Female / Humans Idioma: En Revista: Nat Commun Ano de publicação: 2014 Tipo de documento: Article