2014 Fiscal Year Annual Research Report
| Project/Area Number |
24590582
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| Research Institution | The University of Tokyo |
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Principal Investigator |
植松 智 東京大学, 医科学研究所, 特任教授 (50379088)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 粘膜免疫 / 自然免疫 / Toll-like receptor |
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| Outline of Annual Research Achievements |
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.
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Research Products
(11 results)
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[Journal Article] MyD88 Signaling Inhibits Protective Immunity to the Gastrointestinal Helminth Parasite Heligmosomoides polygyrus.2014
Author(s)
Reynolds LA, Harcus Y, Smith KA, Webb LM, Hewitson JP, Ross EA, Brown S, Uematsu S, Akira S, Gray D, Gray M, MacDonald AS, Cunningham AF, Maizels RM.
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Journal Title
J Immunol.
Volume: 193(6)
Pages: 2984-93
DOI
Peer Reviewed / Open Access
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[Journal Article] nnate lymphoid cells regulate intestinal epithelial cell glycosylation.2014
Author(s)
Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II, Lamichhane A, Takeyama N, Kamioka M, Sakamoto M, Matsuki T, Setoyama H, Imaoka A, Uematsu S, Akira S, Domino SE, Kulig P, Becher B, Renauld JC, Sasakawa C, Umesaki Y, Benno Y, Kiyono H.
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Journal Title
Science.
Volume: 345(6202)
Pages: 1254009
DOI
Peer Reviewed / Open Access
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