| Project/Area Number |
17K08629
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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 |
General medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
Kazuko Miyazaki 京都大学, ウイルス・再生医科学研究所, 研究員 (00311811)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 転写制御 / 遺伝子発現制御 / Treg / 制御性T細胞 / E2A, Id2, Id3 |
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| Outline of Final Research Achievements |
The analysis of gene expression profiles and open chromatin regions in Id2/Id3-deficient Treg cells demonstrated that a set of effector molecules in effector Treg (eTreg) cells could be regulated by E-Id3 protein axis. Then, we examined the chromatin interactions in CXCR5 gene locus, which was one of the activation-related genes in eTreg cells and could be the direct target of E2A. From the result of Hi-C analysis that CXCR5 gene resided in the permissive “A” compartment in resting cells, we conclude that Id-proteins possibly function as a gatekeeper of eTreg cell differentiation.
In addition, we proved that Id2 and Id3 expression in Treg cells plays an important role in the suppression of systemic inflammation not only in childhood but also in adulthood, which was revealed by the analysis of Id2-/Id3-flox Foxp3Cre/DTR mouse line.
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| Academic Significance and Societal Importance of the Research Achievements |
Treg細胞におけるエンハンサー機能調節の制御機構をゲノムワイドに解析した結果は、アレルギー反応の抑制における転写制御のメカニズムの解明につながり、社会的意義が深いと思われる。また、作成された新規マウスモデルで、Id2/Id3による Treg細胞の機能制御が全身性の炎症抑制に必須であることを証明したことは、学術的に意義深い。それを用いて、成獣期において実際にどのようにTh2炎症が起こるのかを詳細に解析することが可能になり、今後の研究の発展が期待できる。
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