| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Outline of Final Research Achievements |
Radiation-induced intestinal fibrosis (RIF) is a serious complication after abdominal radiotherapy. Abdominal irradiation induced fibrosis of the submucosa associated with the excessive accumulation of eosinophils. Eosinophil-deficiency markedly ameliorated submucosal fibrosis post-irradiation. Irradiation elevated extracellular adenosine triphosphate levels, which in turned induced CCL11 and GM-CSF expression by submucosal pericryptal α-SMA+ cells that attracted and activated eosinophils, respectively. TGF-β from GM-CSF-stimulated eosinophils promoted collagen expression by α-SMA+ cells. Treatment with a newly developed IL-5 receptor alpha-targeting antibody, analogous to the human agent benralizumab, depleted intestinal eosinophils and suppressed radiation-induced submucosal fibrosis effectively. Collectively, we identified eosinophils as a crucial factor in the pathogenesis of RIF and showed a new therapeutic strategy for RIF targeting on eosinophils.
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