| First Author | Takemura N | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 3492 | PubMed ID | 24637670 |
| Mgi Jnum | J:210311 | Mgi Id | MGI:5570451 |
| Doi | 10.1038/ncomms4492 | Citation | Takemura N, et al. (2014) Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. Nat Commun 5:3492 |
| abstractText | 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. |
