Identification of microbiota-derived metabolites that regulate the host immunity
| Project/Area Number |
18H04028
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
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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 |
¥44,200,000 (Direct Cost: ¥34,000,000、Indirect Cost: ¥10,200,000)
Fiscal Year 2020: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2018: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
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| Keywords | 粘膜免疫 / 腸内細菌 / 代謝物 / 腸管免疫 |
|---|
| Outline of Final Research Achievements |
Small intestinal mononuclear cells expressing CX3CR1 (CX3CR1+ cells) uptake luminal antigens by protruding their dendrites into the lumen. Mice lacking GPR31, which was highly and selectively expressed in intestinal CX3CR1+ cells, showed defective dendrite protrusions of CX3CR1+ cells in the small intestine. We purified a GPR31-activating fraction of intestinal content. Both lactic acid and pyruvic acid induced dendrite extension of CX3CR1+ cells of wild-type mice, but not GPR31-deficient mice. Oral administration of lactate/pyruvate enhanced dendrite protrusion of CX3CR1+ cells in the intestine of wild-type mice, but not GPR31-deficient mice. Lactate/pyruvate-treated wild-type mice showed enhanced immune response and high resistance to intestinal Salmonella infection. Thus, lactate/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 |
近年腸内細菌叢が我々宿主の生理機能に重要な役割を担っていることが明らかになってきた。しかしながら、消化管腔という体外で、腸管上皮のバリア機能により宿主細胞に接することなく棲息する腸内細菌叢が、宿主に作用するメカニズムは明らかになっていなかった。本研究で、腸内細菌叢が消化管腔で産生する代謝産物を介して宿主に作用していることが明らかになった。さらに、乳酸・ピルビン酸の経口投与が、消化管免疫系の強化につながることを明らかにしたことは、今後経口免疫強化剤の開発に資する成果と考えられる。
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] Oral intake of silica nanoparticles exacerbates intestinal inflammation.2021
Author(s)
Ogawa T, Okumura R, Nagano K, Minemura T, Izumi M, Motooka D, Nakamura S, Iida T, Maeda Y, Kumanogoh A, Tsutsumi Y, Takeda K
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Journal Title
Biochem Biophys Res Commun
Volume: 534
Pages: 540-546
DOI
Related Report
Peer Reviewed
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[Journal Article] Human NKp44+ ILC3 character associated with induction of tumor-associated tertiary lymphoid structures is altered in T3/T4 colorectal cancer.2020
Author(s)
Ikeda A, Ogino T, Kayama H, Okuzaki D, Nishimura J, Fujino S, Miyoshi N, Takahashi H, Uemura M, Matsuda C, Yamamoto H, Takeda K, Mizushima T, Mori M, Doki Y
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Journal Title
Cancer Immunol. Res
Volume: in press
Issue: 6
Pages: 724-731
DOI
Related Report
Peer Reviewed
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[Journal Article] Novel mass spectrometry-based comprehensive lipidomic analysis of plasma from patients with inflammatory bowel disease.2020
Author(s)
Iwatani S, Iijima H, Otake Y, Amano T, Tani M, Yoshihara T, Tashiro T, Tsujii Y, Inoue T, Hayashi Y, Takeda K, Hayashi A, Fujita S, Shinzaki S, Takehara T.
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Journal Title
J Gastroenterol Hepatol.
Volume: -
Issue: 8
Pages: 1355-1364
DOI
Related Report
Peer Reviewed
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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] Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.2018
Author(s)
Kayama H, Kohyama M, Okuzaki D, Motooka D, Barman S, Okumura R, Muneta M, Hoshino K, Sasaki I, Ise W, Matsuno H, Nishimura J, Kurosaki T, Nakamura S, Arase H, Kaisho T, Takeda K.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 115
Issue: 33
Pages: 8418-8423
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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