Immunological memory formation through nuclear receptors and its application for vaccine therapy
| Project/Area Number |
17H03928
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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 |
Integrative animal science
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| Research Institution | Hokkaido University |
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Principal Investigator |
Takada Kensuke 北海道大学, 獣医学研究院, 准教授 (40570073)
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| Co-Investigator(Kenkyū-buntansha) |
稲葉 睦 北海道大学, 獣医学研究院, 教授 (00183179)
山崎 淳平 北海道大学, 獣医学研究院, 特任准教授 (20732902)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | T細胞 / 核内受容体 / 免疫記憶 / 生体防御 / ワクチン / 動物生命科学 |
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| Outline of Final Research Achievements |
The detailed mechanism of immunological memory, the basic principle of vaccines, has not yet been elucidated. In this study, we focused on the ROR family nuclear receptor, which shows a marked increase in expression during memory CD8+ T lymphocyte differentiation, and investigated the involvement of this molecule in the regulation of memory T lymphocyte differentiation and function. It was clarified that RORalpha affects the survival of activated T lymphocytes and effector differentiation by regulating of the expression of cholesterol metabolism-related genes. Furthermore, we obtained the preliminary finding that RORalpha may be involved with the immune response of memory CD8+ T lymphocytes to infection, which prompts us for further examinations in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
過去に感染した病原体の再感染に対し、免疫系はより素早く強力に応答する（免疫記憶）。免疫記憶の本体は抗原特異的な応答の後、体内で長期間維持される記憶リンパ球である。ウイルスや細菌、腫瘍細胞に対する防御を担うTリンパ球の記憶メカニズムを解明することは、ワクチン・免疫療法の開発基盤として医学・獣医学に資する。本研究から、リガンド依存的な転写制御因子である核内受容体RORalphaがCD8+ Tリンパ球の免疫応答と機能分化に関与することが明らかとなった。RORalphaの活性は合成リガンドを使って制御が可能であることから、本研究の知見は、当該因子を標的とした新たな免疫療法の開発につながり得る。
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Report
(5 results)
Research Products
(9 results)
