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

• DOI: 10.1038/ncomms4492
• Publication Date: 2014-03-18T10:49:30Z
• Authors: Naoki Takemura; Takumi Kawasaki; Jun Kunisawa; Shintaro Sato; Aayam Lamichhane; Kouji Kobiyama; Taiki Aoshi; Junichi Ito; Kenji Mizuguchi; Thangaraj Karuppu...; Kouta Matsunaga; Shoichiro Miyatake; Nobuko Mori; Tohru Tsujimura; Takashi Satoh; Yutaro Kumagai; Taro Kawai; Daron M. Standley; Ken J. Ishii; Hiroshi Kiyono; Shizuo Akira; Satoshi Uematsu
• Keywords: TLR3

High-dose ionizing radiation induces severe DNA damage in the epithelial stem cells small intestinal crypts and causes gastrointestinal syndrome (GIS). Although tumour suppressor p53 is a primary factor inducing death of crypt with damage, its essential role maintaining genome stability means inhibiting to prevent GIS not viable strategy. Here we show that innate immune receptor Toll-like 3 (TLR3) critical for pathogenesis GIS. Tlr3(-/-) mice substantial resistance owing significantly reduced radiation-induced cell death. Despite showing death, p53-dependent impaired mice. leakage cellular RNA, which extensive via TLR3. An inhibitor TLR3-RNA binding ameliorates by reducing Thus, propose blocking TLR3 activation as novel approach treat