| Project/Area Number |
18K07971
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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 | Shimane University |
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Principal Investigator |
Ishihara Shunji 島根大学, 学術研究院医学・看護学系, 教授 (80263531)
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| Co-Investigator(Kenkyū-buntansha) |
三島 義之 島根大学, 学術研究院医学・看護学系, 助教 (30397864)
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 制御性B細胞 / ATP / クローン病 / 潰瘍性大腸炎 / IL-10 / 自然免疫 / Crohn病 / アデノシン三リン酸 / 腸管免疫 / P2X7受容体 / アデノシン三リン酸（ATP） |
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| Outline of Final Research Achievements |
Regulatory B cells (Breg) dysfunction is associated with the pathogenesis of Crohn's disease (CD), but its mechanism is unknown. We focused on extracellular adenosine triphosphate (ATP) produced in colitis tissues and examined its effect on Breg dysfunction in CD patients.
B cells isolated from the spleen of mice were cultured and various concentration of ATP was added to the culture system. The effect of ATP on IL-10 induced by various bacterial antigens was examined, showing that IL-10 production by B cells was suppressed depending on the ATP concentration. We also examined the effect of ATP on IL-10 production by B cells isolated from the mesenteric lymph nodes of ATP receptor P2X7-deficient mice. As a result, the decrease in IL-10 production due to ATP was recovered by P2X7 receptor deficiency in B cells. Thus, ATP reduces IL-10 production via the P2X7 receptor of B cells, suggesting that this mechanism may be involved in Breg dysfunction in association with the pathogenesis of CD.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、様々な自己免疫疾患において、CD同様にBregの機能異常が病態に関わる示されてきた。しかし各々の疾患で「なぜBregの機能が低下しているのか？」という疑問を解明する研究はおこなわれていない。今回、私共が着目した「細胞外ATPによる Bregの機能減弱」に関する報告は国内外を通じて皆無である。Bregの機能低下機序を明らかにし、そのメカニズムが特異的にCDの病態に関わること、あるいは本メカニズム深く関わるCDのポピュレーションが存在すること検証できれば、本研究の成果は、これまでと異なる視点からの新知見となり、将来の新規治療開発につながっていくと思われる。
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