| Project/Area Number |
18K07898
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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 53010:Gastroenterology-related
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| Research Institution | Chiba University |
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Principal Investigator |
FUJIMURA LISA 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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| 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)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 腸管神経 / 好酸球 / IL5 / 腸炎 / 腸管免疫 / IgA |
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| Outline of Final Research Achievements |
We analyzed relation of enteric neurons (EN) and intestinal barrier using Ncx KO mice in which EN were increased. We demonstrated that eosinophils (Eo) increased in lamina propria (LP) of Ncx KO mice small intestine (SI) compared to those of WT mice. Expression of IL5 was higher in the intestinal tissues from Ncx KO than that from WT.
In order to examine whether IL5 is responsible for increased number of Eo in Ncx KO mice LP, we generated IL5 KO mice in Ncx KO background. FACS analysis revealed that mature Eo in LP was decreased in IL5/Ncx double KO mice compared to those of Ncx KO mice. As a result, the total Eo was decreased in double KO mice. These data indicated that high amount of IL5 expression in SI is responsible for mature Eo generation in Ncx KO mice. To elucidate that EN could products IL5, Immunohistology revealed that EN express IL5. We are currently investigating the mechanism of IL5 production from EN and biological significance of increased number of Eo in Ncx KO mice.
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| Academic Significance and Societal Importance of the Research Achievements |
非常に高い防御機能をもつ腸管では、上皮系・内分泌系・免疫系・神経系・腸内細菌叢が相互作用を行い恒常性を維持している。それらのバランスが崩れると、腸炎などの機能異常が起こると考えられている。近年、粘膜に存在する神経系が免疫系細胞と解剖学的に非常に近接していること、それらが相互作用を行っていて、その破綻は炎症やアレルギーの原因であると報告されているが、ごく少数である。また、近年わが国で増加傾向にある潰瘍性大腸炎やクローン病などの難治性腸疾患の発症や病態は、多大なストレスと関連があるといわれており、神経系-免疫系相互作用の解明とその破綻による腸炎の病態解明における本研究は、非常に意義がある。
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