ID 112347
著者
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
松本, 満 Tokushima University|Japan Agency for Medical Research and Development 徳島大学 教育研究者総覧 KAKEN研究者をさがす
キーワード
Medullary thymic epithelial cell (mTEC)
AIRE
Muscle
Tolerance
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Journal of Autoimmunity
ISSN
08968411
cat書誌ID
AA10717368
AA11542328
出版者
Elsevier
86
開始ページ
75
終了ページ
92
発行日
2017-09-18
権利情報
© 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
333662
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所
医学系
病院