ID | 112347 |
Author |
Kajimoto, Tatsuya
Tokushima University
Matsuoka, Yoshiki
Tokushima University
Mouri, Yasuhiro
Tokushima University
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Morimoto, Junko
Tokushima University
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Nishioka, Yasuhiko
The University of Tokushima
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Uehara, Hisanori
The University of Tokushima
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Izumi, Keisuke
The University of Tokushima
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Tsuneyama, Koichi
The University of Tokushima
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Hosomichi, Kazuyoshi
Kanazawa University
Shiraki, Ayako
Tokyo University of Agriculture and Technology
Shibutani, Makoto
Tokyo University of Agriculture and Technology
Mitsumori, Kunitoshi
Tokyo University of Agriculture and Technology
Matsumoto, Mitsuru
Tokushima University|Japan Agency for Medical Research and Development
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Keywords | Medullary thymic epithelial cell (mTEC)
AIRE
Muscle
Tolerance
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Content Type |
Journal Article
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Description | Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire.
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Journal Title |
Journal of Autoimmunity
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ISSN | 08968411
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NCID | AA10717368
AA11542328
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Publisher | Elsevier
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Volume | 86
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Start Page | 75
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End Page | 92
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Published Date | 2017-09-18
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Rights | © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Publisher
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departments |
Institute of Advanced Medical Sciences
Medical Sciences
University Hospital
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