研究課題
High-dose ionizing radiation induces severe DNA damage in the epithelial stem cells in small intestinal crypts and causes gastrointestinal syndrome (GIS). Last year, we showed that the innate immune receptor Toll-like receptor 3 (TLR3) is critical for the pathogenesis of GIS. An inhibitor of TLR3–RNA binding ameliorates GIS by reducing crypt cell death. This year, we checked toxicity and stability analysis of the inhibitor and started collaboration with a company for development of new therapy for GIS.Radiation-induced intestinal fibrosis (RIF) is permanent and irreversible disease condition which frequently occurs among patients received abdominal radiation therapy. Here we show that RIF is caused by unique mechanisms that are driven solely by intestinal resident cells. A single-dose irradiation induced small intestinal submucosal fibrosis associated with excessive accumulation and degranulation of intestinal eosinophils. In irradiated intestine, long-term spontaneous crypt cell death caused elevation of extracellular ATP, which activated pericryptal myofibroblasts to express eosinophil chemoattractant CCL11. Eosinophil-deficient ΔdblGATA mice showed significant attenuation in RIF, suggesting that eosinophils play essential role for RIF.
すべて 2015 2014
すべて 雑誌論文 (4件) (うち査読あり 4件、 オープンアクセス 4件) 学会発表 (4件) 図書 (3件)
J Biol Chem.
巻: pii: jbc.M114.631374. ページ: 1-19
J Immunol.
巻: 193(6) ページ: 2984-93
10.4049/jimmunol.1401056.
Science.
巻: 345(6202) ページ: 1254009
10.1126/science.1254009.
Eur J Immunol.
巻: 45(2) ページ: 513-24
10.1002/eji.201444744.
