| Project/Area Number |
18K06951
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坂本 明美 千葉大学, バイオメディカル研究センター, 准教授 (90359597)
藤村 理紗 千葉大学, バイオメディカル研究センター, 助教 (30376363)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 腸管神経 / 腸管免疫 / 腸内細菌 / Hirschsprung病類縁疾患 / Ncx KOマウス / 好酸球 / 腸内細菌叢 / 無菌マウス / Neuromedin U / IL5 / IL-5 / 腸内フローラ |
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| Outline of Final Research Achievements |
Enteric neurons play critical roles in the regulation of intestinal homeostasis. We demonstrated that Ncx KO mice which have a large number of enteric neurons have high susceptibility to DSS induced colitis due to epithelial hyperpermeability and dysbiosis. In this study, we investigated the mucosal immunity in Ncx KO mice. FACS analysis revealed that the percentage of eosinophils in lamina propria of small intestine (SI) in Ncx KO mice was significantly higher than that in wild type (WT) mice. IL5 and neuromedin U mRNAs were upregulated in SI of Ncx KO mice compared to those of WT mice. Furthermore, IL5 was upregulated in the ILC2 cell population, suggesting activation of Neuromedin U-ILC2-IL5 axis. In order to elucidate the role of eosinophils in Ncx KO mice, we deleted eosinophils by creating Ncx KO /dblGATA double KO (DKO) mice and induced DSS enterocolitis. The increased mortality in DKO mice suggested that eosinophils play a protective role in the intestine of Ncx KO mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は腸管神経増加により腸管免疫系やバリア機構に異常をきたすことを明らにし、腸管神経の数はその発生・分化過程で厳密に制御される必要があることを示した。腸管神経増加状態にあるNcx KOマウスでは腸管粘膜固有層の好酸球増加が腸管炎症に対して保護的に機能することを示したものであり、これまで腸管好酸球が炎症促進的に機能するという報告が多かったが腸管好酸球の多様性を示したものである。今後炎症性腸疾患・好酸球性腸炎などの炎症疾患や腸管アレルギー疾患などの発症機序や病態が明らかできる可能性がありさらに腸管神経系をターゲットとした新たな治療、予防法が確立できその成果の臨床的・社会的意義は大きい。
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