| Project/Area Number |
17K08892
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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 | Toho University |
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Principal Investigator |
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 翻訳後修飾 / リンパ球機能 / アセチル化 / B細胞分化 / アセチル化修飾 / B細胞成熟 |
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| Outline of Final Research Achievements |
Interleukin-7 (IL-7) is essential for lymphocyte development. To identify functional subdomains in the cytoplasmic tail of IL-7 receptor alpha (IL-7Ra) chain, here, we constructed a series of IL-7Ra deletion mutants. We found that IL-7Ra-deficient hematopoietic progenitor cells (HSCs) gave rise to B cells both in vitro and in vivo when a wild-type (WT) IL-7Ra chain was introduced; however, no B cells were observed under the same conditions from IL-7Ra-deficient HSCs with introduction of exogenous IL-7Ra subunit, which lacked the amino acid region at position 414-441 (d414-441 mutant). Signal transducer and activator of transcription 5 (Stat5) was phosphorylated in cells with d414-441 mutant, similar to that in WT cells, in response to IL-7 stimulation. In contrast, more truncated Stat5 was generated in cells with d414-441 mutant in WT cells. These results suggested that amino acid 414-441 in IL-7Rα chain formed a critical subdomain necessary for role of IL-7 in B cell development.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究成果は、インターロイキン-7受容体に新しい機能ドメインが存在することを示した。本検討の結果から、このドメインがアセチル化修飾を介した情報伝達系分子の機能調節に関わる可能性が示唆された。免疫系細胞の情報伝達異常は免疫不全や白血病等の疾病に至ることがある。こうした疾患の治療開発へつながる可能性が本研究の成果の意義と考えている。本検討で見出したアセチル化の分子機構の全貌を明らかにすること、免疫系を含めた細胞のライフサイクルにおいて、アセチル化がどの過程にどのように関与しているかを明らかにすることも重要となる。基礎分野にこうした気付きを残せた点でも学問的意義があったと考えている。
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