ID 112347
Author
Kajimoto, Tatsuya Tokushima University
Matsuoka, Yoshiki Tokushima University
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 Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
Medullary thymic epithelial cell (mTEC)
AIRE
Muscle
Tolerance
Content Type
Journal Article
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.
Journal Title
Journal of Autoimmunity
ISSN
08968411
NCID
AA10717368
AA11542328
Publisher
Elsevier
Volume
86
Start Page
75
End Page
92
Published Date
2017-09-18
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/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences
Medical Sciences
University Hospital