| Project/Area Number |
18K07189
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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 49070:Immunology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Satoh-Takayama Naoko 国立研究開発法人理化学研究所, 生命医科学研究センター, 専任研究員 (90732446)
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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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 自然リンパ球 / 免疫 / 粘膜免疫 / 分化・機能メカニズム / ILCs / PD-1を介した制御 / 免疫学 |
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| Outline of Final Research Achievements |
The intestinal microbiota shapes and directs immune development locally and systemically, but little is known about whether commensal microbes in the stomach can impact their immunological microenvironment. Here, we report that ILC2s are the predominant ILC subset in the stomach and show that their homeostasis and effector functions are regulated by local commensal communities. Microbes can elicit IL-7 and IL-33 production in the stomach, which in turn trigger ILC2s. Stomach ILC2s are also rapidly induced following infection with Helicobacter pylori. ILC2-derived IL-5 results in the production of IgA, which coats stomach bacteria in both SPF and H. pylori-infected mice. Our study thus identifies a novel ILC2-dependent IgA response that is regulated by the commensal microbiota and is implicated in stomach barrier function.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで胃は食物を貯蔵・分解する機能のみを主体とする臓器であるという認識で、免疫学的な意義については低いと考えられてきた。しかしながら、本研究により胃の持つ防御的な役割に加え、胃に存在する細菌叢の重要性と免疫応答との関連性について明らかにすることができ、恒常性を維持する需要な要になりうる知見であると、一石を投じた。また本研究により、ピロリ感染後に生じるB細胞集積は、悪性リンパ腫の一種であるMALTとの関連性が示唆されており、この発生メカニズムを明らかにする事は、胃ガンの予防・治療に繋がることが期待できる。
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