Studies on the mechanisms for autoimmune phenotype in disease model mouse
| 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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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Ectopic Aire expression in 1 the thymic cortex reveals inherent properties of Aire as a tolerogenic factor within the medulla2015
Author(s)
Nishijima H, Kitano S, Miyachi H, Morimoto J, Kawano H, Hirota F, Morita R, Mouri Y, Masuda K, Imoto I, Ikuta K, Matsumoto M.
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Journal Title
J Immunol
Volume: 195
Issue: 10
Pages: 4641-4649
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] NIK in thymic stroma establishes central tolerance by orchestrating cross-talk with not only thymocytes but also dendritic cells2014
Author(s)
Mouri, Y., Nishijima, H., Kawano, H., Hirota, F., Sakaguchi, N., Morimoto, J., Matsumoto, M.
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Journal Title
J. Immunol.
Volume: 193
Issue: 9
Pages: 4356-4367
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Unexpected disturbance of the development of medullary thymic epithelial cells at immature stages by the long-term ablation of mature Aire-expressing cells2014
Author(s)
Kawano, H., Morimoto, J., Mouri, Y., Nishijima, H., Nishioka, Y., Matsumoto, M.
Organizer
第43回日本免疫学会総会
Place of Presentation
京都国際会議場（京都府・京都市）
Year and Date
2014-12-10 – 2014-12-12
Related Report
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[Presentation] Approaches to identify Aire-regulated non-tissue-restricted antigen genes by the ectopic expression of Aire in thymic cortex2014
Author(s)
Nishijima, H., Morimoto, J., Mouri, Y., Kawano, H., Ikuta, K., Matsumoto, M.
Organizer
第43回日本免疫学会総会
Place of Presentation
京都国際会議場（京都府・京都市）
Year and Date
2014-12-10 – 2014-12-12
Related Report
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[Presentation] Ectopic Aire expression in thymic cortex reveals inherent properties of Aire as a stromal factor for medullary thymic microenvironment2014
Author(s)
Nishijima, H., Morimoto, J., Kawano, H., Mouri, Y., Ikuta, K., Matsumoto, M.
Organizer
ThymOz 7
Place of Presentation
Heron Island (Australia)
Year and Date
2014-04-02 – 2014-04-07
Related Report
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