Studies aiming the establishing self-tolerance for the cure of autoimmune disease
Project/Area Number |
25293223
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Collagenous pathology/Allergology
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Research Institution | The University of Tokushima |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
NISHIJIMA Hitoshi 徳島大学, 疾患酵素学研究センター, 助教 (60425410)
MOURI Yasuhiro 徳島大学, 疾患酵素学研究センター, 助教 (80464353)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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Keywords | AIRE / thymus / autoimmunity / 胸腺髄質上皮細胞 / Aire / ノックインマウス / 自己免疫疾患 / 胸腺 |
Outline of Final Research Achievements |
Cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs) play essential roles in the positive and negative selection, respectively. Aire in mTECs plays an essential role in the latter. We used BAC technology to establish a semiknockin strain expressing Aire under control of the promoter of β5t, a thymoproteasome expressed exclusively in the cortex. Although Aire was expressed in cTECs as typical nuclear dot protein, cTECs expressing Aire ectopically did not confer transcriptional expression of Aire-dependent tissue-restricted antigen genes. We also established a novel Aire reporter strain in which endogenous Aire is replaced by the human AIRE-GFP-Flag tag gene. The hAGF reporter protein was produced and retained very efficiently within mTECs as authentic Aire nuclear dot protein. Remarkably, snapshot analysis revealed that mTECs expressing hAGF accounted for >95% of mature mTECs, suggesting that Aire expression does not represent a particular mTEC lineage(s).
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Report
(4 results)
Research Products
(27 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 medulla.2015
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
Pages: 4641-4649
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease.2015
Author(s)
Yoshida S, Aihara K, Ikeda Y, Sumitomo-Ueda Y, Uemoto R, Ishikawa K, Ise T, Yagi S, Iwase T, Mouri Y, Sakari M, Matsumoto T, Takeyama K, Akaike M, Matsumoto M, Sata M, Walsh K, Kato S, Matsumoto T.
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Journal Title
Int Heart J.
Volume: 128
Pages: 105-109
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] NF-kB-induced kinase in thymic stroma establishes central tolerance by orchestrating cross-talk with not only thymocytes but also dendritic cells.2014
Author(s)
Mouri, Y., Nishijima, H., Kawano, H., Hirota, F., Sakaguchi, N., Morimoto, J., Matsumoto, M.
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Journal Title
Journal of Immunology
Volume: 193
Pages: 4356-4367
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Temporal Lineage Tracing of Aire-Expressing Cells Reveals a Requirement for Aire in Their Maturation Program2014
Author(s)
Nishikawa, Y., Nishijima, H., Matsumoto, M., Morimoto, J., Hirota, F., Takahashi, S., Luche, H., Fehling, H.J., Mouri, Y., Matsumoto, M.
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Journal Title
J Immunol.
Volume: 192
Pages: 2585-2592
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] TGF-β type II receptor expression in thymic epithelial cells inhibits the development of Hassall’s corpuscles in mice2013
Author(s)
Odaka, C., Hauri-Hohl, M., Takizawa, K., Nishikawa, Y., Yano, M., Matsumoto, M., Boyd, R., Hollander, G.A.
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Journal Title
Int. Immunol.
Volume: 25
Pages: 633-642
DOI
Related Report
Peer Reviewed
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[Journal Article] Which model better fits the role of Aire in the establishment of self-tolerance: the transcription model or the maturation model?2013
Author(s)
Matsumoto, M., Nishikawa, Y., Nishijima, H., Morimoto, J., Matsumoto, M., Mouri, Y.
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Journal Title
Front. Immunol.
Volume: 4
Pages: 210-210
DOI
Related Report
Peer Reviewed
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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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[Presentation] Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program2013
Author(s)
Matsumoto, M., Nishikawa, Y., Nishijima, H., Matsumoto, M., Morimoto, J., Hirota, F., Takahashi, S., Luche, H., Fehling, H.J., Mouri, Y.
Organizer
The 6th International Workshop of Kyoto T Cell Conference
Place of Presentation
芝蘭会館(京都府)
Related Report
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[Presentation] Requirement of Aire expression within thymic medulla but not cortex for establishing self-tolerance
Author(s)
Nishijima, H., Morimoto, J., Mouri, Y., Nishikawa, Y., Ikuta, K., Matsumoto, M.
Organizer
第42回日本免疫学会総会
Place of Presentation
幕張メッセ(千葉県)
Related Report
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