| Project/Area Number |
15K06796
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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 |
Laboratory animal science
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| Research Institution | Nihon Pharmaceutical University (2017)
Hirosaki University (2015-2016) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
土田 成紀 弘前大学, 医学研究科, 客員研究員 (20142862)
七島 直樹 弘前大学, 保健学研究科, 講師 (80333730)
清水 武史 弘前大学, 医学研究科, 助教 (90374818)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | CD4+T細胞 / 分化 / 胸腺 / レチノイン酸 / 脾臓 / 胸腺DP細胞 / レチノイン酸受容体 / Egr1 / Cryab / Dec1 / NF-kB / Gata3 / ヘルパーT細胞の分化 / Fog1 / Gata3遺伝子プロモーター / クロマチン構造 / SDラット (SDR) / 弘前ヘアレスラット (HHR) |
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| Outline of Final Research Achievements |
In this study, it was revealed that retinoic acid (RA)-reactivity in thymic CD4+CD8+ (DP) T cells is important for proper differentiation of CD4+ T cells. We suggested the possible pathway that RA upregulates expression of its target gene Cryab which is involved in NF-kB activation and nuclear translocation, and activated NF-kB then induce expression of the Gata3 gene, a master regulator of CD4+ T cell-differentiation. It was also shown that thymic dendritic cells are implicated in acquisition of the RA-reactivity of CD4+ T cells in the thymus.
We also demonstrated that high level of expression of the Gata3 gene observed in thymic DP T cells is downregulated in subsequent differentiation stages of CD4+ T cells and alternation of histone modification status in the upstream promoter region of the gene is responsible for the downregulation.
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