| Project/Area Number |
17K17005
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatric surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
Ochi Takanori 順天堂大学, 医学部, 准教授 (70794147)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | マクロファージ / 小腸 / IL-10 / NSAIDs / 小腸炎 / アミノ酸 / NSAID / インターロイキン-10 |
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| Outline of Final Research Achievements |
The intestine contains the largest pool of macrophages (Mφs), which produce anti-inflammatory cytokine interleukin-10 (IL-10) and play an important role in the maintenance of gastrointestinal homeostasis. We have previously reported that IL-10-producing Mφs reside in the small intestine (SI) were regulated by dietary antigens, especially amino acids, while colonic Mφs were regulated by the gut microbiota. In this study, we showed that SI Mφs regulate epithelial barrier integrity via the secretion of IL-10. Notably, IL-10-producing Mφs play an essential role in the recovery from acute SI injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Since the development and function of anti-inflammatory Mφs in the SI appear to be regulated by dietary antigens, optimal dietary interventions could be used to promote mucosal healing in the SI, leading to reduce the risk of severe enteritis in the patients with short bowel syndrome requiring total parenteral nutrition.
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| Academic Significance and Societal Importance of the Research Achievements |
小腸において炎症抑制能を有するマクロファージが食餌性抗原、特にアミノ酸により誘導されること、小腸常在マクロファージがIL-10を産生して小腸粘膜上皮バリアの健全性を制御していることから、IL-10産生マクロファージを誘導する食餌性抗原を選択的に投与することで、小腸粘膜上皮修復が促進され、例えば短腸症候群や炎症性腸疾患などの患児において重症腸炎発症リスクを低減する新たな治療戦略に繋がるものと考える。
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