Recognition of bacterial metabolites by GPCR expressed on intestinal phagocytes
| Project/Area Number |
16K08838
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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 |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
Umemoto Eiji 大阪大学, 医学系研究科, 准教授 (90452440)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 粘膜免疫 / 腸内細菌 / 生理活性分子 / マクロファージ / G蛋白質共役型受容体 / 腸管免疫 / 貪食細胞 / 脂質 |
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| Outline of Final Research Achievements |
Small intestinal mononuclear cells expressing CX3CR1 (CX3CR1+ cells) uptake luminal antigens by protruding their dendrites into the lumen. We showed that bacterial metabolites, pyruvic acid/lactic acid, induce dendrite protrusion via GPR31 in CX3CR1+ cells. Oral administration of lactate and pyruvate enhanced dendrite protrusion of CX3CR1+ cells in the small intestine of wild-type mice, but not GPR31-deficient mice. In addition, lactate/pyruvate-treated wild-type mice showed enhanced immune response and high resistance to intestinal Salmonella infection. These findings demonstrate that lactate and pyruvate, which are produced in the intestinal lumen in a bacteria-dependent manner, contribute to enhanced immune responses by inducing GPR31-mediated dendrite protrusion of intestinal CX3CR1+ cells.
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| Academic Significance and Societal Importance of the Research Achievements |
数ある腸内細菌由来の代謝分子の中で、生理活性を有する分子の実体およびその生理的役割については不明な点が多い。特に腸管の免疫細胞が乳酸・ピルビン酸の受容体を持つことはこれまで知られておらず、乳酸・ピルビン酸がG蛋白質共役型受容体を介して腸管の免疫細胞に作用する仕組みを解明した本研究の成果は、腸内細菌と免疫細胞との相互作用を理解する上で重要だと考えられる。
本研究により、乳酸やピルビン酸の摂取が病原性細菌に対する免疫応答を高める可能性が明らかになったことから、乳酸・ピルビン酸およびGPR31は免疫機能活性化の新たな標的として、今後、腸内細菌叢の改善や効果的な経口ワクチン開発への応用等が考えられる。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites.2019
Author(s)
Morita N, Umemoto E, Fujita S, Hayashi A, Kikuta J, Kimura I, Haneda T, Imai T, Inoue A, Mimuro H, Maeda Y, Kayama H, Okumura R, Aoki J, Okada N, Kida T, Ishii M, Nabeshima R, Takeda K
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Journal Title
nature
Volume: 566
Issue: 7742
Pages: 110-114
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells.2017
Author(s)
Ikeda K, Kinoshita M, Kayama H, Nagamori S, Kongpracha P, Umemoto E, Okumura R, Kurakawa T, Murakami M, Mikami N, Shintani Y, Ueno S, Andou A, Ito M, Tsumura H, Yasutomo K, Ozono K, Takashima S, Sakaguchi S, Kanai Y, Takeda K.
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Journal Title
Cell Reports
Volume: 21
Issue: 7
Pages: 1824-1838
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] E-NPP3 controls plasmacytoid dendritic cell numbers in the small intestine.2017
Author(s)
Furuta, Y., Tsai, S-H., Kinoshita, M., Fujimoto, K., Okumura, R., Umemoto, E., Kurashima, Y, Kiyono, H., Kayama, H., Takeda, K.
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Journal Title
Mucosal Immunology
Volume: 12
Issue: 2
Pages: e0172509-e0172509
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine.2016
Author(s)
Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, Hirota K, Matsushita M, Furuta Y, Narazaki M, Sakaguchi N, Kayama H, Nakamura S, Iida T, Saeki Y, Kumanogoh A, Sakaguchi S, and Takeda K
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Journal Title
Arthritis Rheum
Volume: 68
Issue: 11
Pages: 2646-2661
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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