IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms4492.html
   My bibliography  Save this article

Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome

Author

Listed:
  • Naoki Takemura

    (International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo)

  • Takumi Kawasaki

    (Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University
    Research Institute for Microbial Diseases, Osaka University
    Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST))

  • Jun Kunisawa

    (Institute of Medical Science, The University of Tokyo
    Laboratory of Vaccine Materials, National Institute of Biomedical Innovation)

  • Shintaro Sato

    (Institute of Medical Science, The University of Tokyo
    Core Research for Evolutional Science and Technology, Japan Science and Technology Agency)

  • Aayam Lamichhane

    (Institute of Medical Science, The University of Tokyo)

  • Kouji Kobiyama

    (Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation
    Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University)

  • Taiki Aoshi

    (Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation
    Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University)

  • Junichi Ito

    (Laboratory of Bioinformatics, National Institute of Biomedical Innovation)

  • Kenji Mizuguchi

    (Laboratory of Bioinformatics, National Institute of Biomedical Innovation)

  • Thangaraj Karuppuchamy

    (Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University
    Research Institute for Microbial Diseases, Osaka University)

  • Kouta Matsunaga

    (International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo)

  • Shoichiro Miyatake

    (Laboratory of Self Defense Gene Regulation, Tokyo Metropolitan Institute of Medical Science)

  • Nobuko Mori

    (Graduate School of Science, Osaka Prefecture University)

  • Tohru Tsujimura

    (Hyogo College of Medicine)

  • Takashi Satoh

    (Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University
    Research Institute for Microbial Diseases, Osaka University)

  • Yutaro Kumagai

    (Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University
    Research Institute for Microbial Diseases, Osaka University)

  • Taro Kawai

    (Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST))

  • Daron M. Standley

    (Laboratory of Systems Immunology, WPI Immunology Frontier Research Center, Osaka University)

  • Ken J. Ishii

    (Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation
    Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University)

  • Hiroshi Kiyono

    (Institute of Medical Science, The University of Tokyo
    Core Research for Evolutional Science and Technology, Japan Science and Technology Agency)

  • Shizuo Akira

    (Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University
    Research Institute for Microbial Diseases, Osaka University)

  • Satoshi Uematsu

    (International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo)

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.

Suggested Citation

  • Naoki Takemura & Takumi Kawasaki & Jun Kunisawa & Shintaro Sato & Aayam Lamichhane & Kouji Kobiyama & Taiki Aoshi & Junichi Ito & Kenji Mizuguchi & Thangaraj Karuppuchamy & Kouta Matsunaga & Shoichiro, 2014. "Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome," Nature Communications, Nature, vol. 5(1), pages 1-15, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4492
    DOI: 10.1038/ncomms4492
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms4492
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms4492?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4492. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.