Regulatory mechanism of immune response through metabolic reprograming of T lymphocytes
| Project/Area Number |
17H04086
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Ehime University |
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Principal Investigator |
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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 |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | T細胞 / 代謝 / 免疫疾患 / 解糖系 / グルタミン代謝 / mTORC1 / Pgam1 / グルタミン / 感染免疫 / がん免疫 / 慢性炎症 / エピジェネティクス / α-ケトグルタル酸 / エピゲノム / 免疫記憶 / 抗腫瘍活性 / 疲弊 / 老化 / 代謝リプログラミング / ヒストン脱メチル化 |
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| Outline of Final Research Achievements |
Although the important roles of metabolism in T cell activation and function have been demonstrated, the regulatory mechanism has not been fully elucidated. Furthermore, the influences of metabolic failure on the T cell-dependent immune response in vivo remain unclear. We therefore the role of glycolysis in the T cell-dependent immune response using T cell-specific Pgam1-deficient mice. Both CD8 and CD4 T cell-dependent immune responses were attenuated by Pgam1 deficiency. T cell-dependent inflammation was ameliorated in Pgam1-deficient mice. The development of regulatory T cells was not affected by the deletion of Pgam1 gene in vitro and in vivo. Glycolysis augments the activation of mTOR complex 1 (mTORC1) and the T-cell receptor (TCR) signals. Glutamine is required to augment glycolysis, increase mTORC1 activity and augment TCR signals. These findings suggest that mTORC1, glycolysis and glutamine affect each other and cooperate to induce T cell proliferation, differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究により、T細胞の機能、T細胞依存的な免疫応答は、代謝によって制御されていることが明らかとなった。さらに、T細胞代謝は、解糖系、グルタミン代謝、mTORC1シグナルが強調して働くことで制御されていることが示された。また、Th1、Th2やTh17細胞などのエフェクター細胞、エフェクター細胞と制御性T細胞、CD4 T細胞とCD8 T細胞など免疫細胞間、免疫応答の違いによって代謝経路が異なっていることが明らかとなった。今回の研究結果から、今後、代謝酵素が免疫疾患の新規治療シーズとなりうると考えられる。
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Report
(4 results)
Research Products
(21 results)
