| Project/Area Number |
26461464
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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 |
Collagenous pathology/Allergology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
NISHIJIMA Hitoshi 徳島大学, 先端酵素学研究所(次世代), 助教 (60425410)
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| Co-Investigator(Kenkyū-buntansha) |
松本 満 徳島大学, 先端酵素学研究所(次世代), 教授 (60221595)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 免疫学 / Aire / 自己免疫疾患 / mTEC / AIRE / 遺伝子改変マウス / 負の選択 |
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| Outline of Final Research Achievements |
Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs) play essential roles in the positive and negative selection of developing thymocytes, respectively. Aire in mTECs plays an essential role in the latter process through expression of tissue-restricted Ags. To determine whether the location of Aire within the medulla is essential or whether Aire could also function within the cortex for establishment of self-tolerance, we established a semi-knockin mice (b5t/Aire-Tg) expressing Aire under control of the promoter of b5t, a thymoproteasome expressed exclusively in the cortex. cTECs expressing Aire ectopically did not confer transcriptional expression of either Aire-dependent or Aire-independent tissue-restricted Ag genes. We then crossed b5t/Aire-Tg mice with Aire-deficient mice, generating a strain in which Aire expression was confined to cTECs. Despite the presence of Aire in cTECs, these mice succumbed to autoimmunity, as did Aire-deficient mice.
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