| Project/Area Number |
12470077
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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 | The University of Tokushima |
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Principal Investigator |
TAKAHAMA Yousuke The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (20183858)
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| Project Period (FY) |
2000 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | T lymphocyte / T cell-receptor / thymus / CCL19 / apoptosis / Nurr77 / Stat3 / Chemokine / 器官構築 / 正と負の選択 / タイムラプス解析 / 遺伝子治療 / MAPキナーゼ / 免疫療法 |
|---|
| Research Abstract |
Signals that regulate the development and selection of T lymphocytes in the thymus have been studied. We have found that T-cell receptor-mediated signals activated Akt, which phosphorylated Nur77 and thereby antagonized Nur77-mediated apoptosis of T cells, suggesting that T-cell receptor-mediated positive and negative selection can be controlled by Akt-mediated phophorylation of Nur77. We have also found that the mice in which Stat3 gene in thymic epithelial cells has been specifically disrupted by the keratin 5 promoter developed severe thymic hypoplasia and exhibited a high susceptibility of the thymus to suboptimal doses of dexamethasone or gamma-irradiation, indicating that Stat3 in thymic epithelial cells plays an essential role in maintaining thymic architecture and thymocyte survival. Moreover, we have found that CCR7-ligand chemokine CCL19 attracted mature T cells out of the fetal thymus organ culture, and that neonatal appearance of circulating T cells was defective in CCR7-deficient mice, indicating that CCR7-dependent pathway of thymic emigration represents a major pathway of neonatal T cell export.
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