Elucidation of gut microbiota-independent IL-10 production mechanism of intestinal macrophages
| Project/Area Number |
17K09393
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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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| Research Field |
Gastroenterology
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| Research Institution | Kitasato University |
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Principal Investigator |
Takeuchi Osamu 北里大学, 北里研究所病院, 部長補佐(研究) (00249997)
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| Co-Investigator(Kenkyū-buntansha) |
小林 拓 北里大学, 北里研究所病院, 副センター長 (10424144)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 腸管マクロファージ / IL-10 / NLRP3 / IL-1R / 炎症性腸疾患 / NLRP-3 / IBD |
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| Outline of Final Research Achievements |
IL-10 production in gut macrophages is microbiota-independent and MyD88-dependent. We focused on the NLRP3 inflammasome pathway, which has been attracting attention in recent years as a pathway involved in the induction of inflammatory response. We examined the mechanism by which intestinal macrophages maintain tolerance while contacting external factors such as gut microbiota, that is, the IL-10 expression mechanism produced by intestinal macrophages. In an experiment using a mouse macrophage cell line, IL-10 production via IL-1β/IL-1R was observed. IL-1β may play a role in promoting IL-10 expression by stimulating IL-1R via the MyD88 pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究結果より、炎症性腸疾患の発症に深く関与する腸管マクロファージの特異的かつ恒常的なIL-10の発現機序の一端が明らかになった。腸管型の抗炎症性マクロファージの特性の一つを見いだせたことにより、in vitroあるいはex vivoでの腸管マクロファージを誘導することが出来る様になる可能性がある。さらに腸管マクロファージの機能異常が病態の中心となっている炎症性腸疾患の治療に応用できるかもしれない。このようなマクロファージの機能異常をレスキューさせて正常化するようなことができれば、画期的な治療戦略に結びつくことも期待できる。
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Report
(4 results)
Research Products
(10 results)
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[Presentation] NUDT15 variance increases DNA-incorporated thiopurine metabolites and lymphocyte apoptosis in patients with Inflammatory Bowel Disease2020
Author(s)
Hiroki Kiyohara, Takahiko Toyonaga, Satoshi Kuronuma, Aito Ueno, Shinji Okabayashi, Ryo Ozaki, Osamu Takeuchi, Sally A. Coulthard, Christopher P,F. Redfern, Hideki Terai, Yoichi Tanaka, Masaru Nakano, Toshifumi Hibi, Taku Kobayashi
Organizer
Congress of European Crohns and Colitis Organisation (ECCO)
Related Report
Int'l Joint Research
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