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ID 114944
タイトル別表記
胸腺および末梢トレランスにおいてAireにより制御される臓器特異的自己免疫応答
Amelioration of diabetes in NOD by additive Aire
著者
松本, 穣 徳島大学大学院医科学教育部(医学専攻) 徳島大学 教育研究者総覧
Hosomichi, Kazuyoshi Kanazawa University
キーワード
Aire
1型糖尿病
Xcr1陽性樹状細胞
NOD
mTEC
type 1 diabetes
Xcr1+ DC
資料タイプ
学位論文
抄録
Tissue-specific autoimmune diseases are assumed to arise through malfunction of two checkpoints for immune tolerance: defective elimination of autoreactive T cells in the thymus and activation of these T cells by corresponding autoantigens in the periphery. However, evidence for this model and the outcome of such alterations in each or both of the tolerance mechanisms have not been sufficiently investigated. We studied these issues by expressing human AIRE (huAIRE) as a modifier of tolerance function in NOD mice wherein the defects of thymic and peripheral tolerance together cause type I diabetes (T1D). Additive huAIRE expression in the thymic stroma had no major impact on the production of diabetogenic T cells in the thymus. In contrast, huAIRE expression in peripheral antigen-presenting cells (APCs) rendered the mice resistant to T1D, while maintaining other tissue-specific autoimmune responses and antibody production against an exogenous protein antigen, because of the loss of Xcr1+ dendritic cells, an essential component for activating diabetogenic T cells in the periphery. These results contrast with our recent demonstration that huAIRE expression in both the thymic stroma and peripheral APCs resulted in the paradoxical development of muscle-specific autoimmunity. Our results reveal that tissue-specific autoimmunity is differentially controlled by a combination of thymic function and peripheral tolerance, which can be manipulated by expression of huAIRE/Aire in each or both of the tolerance mechanisms.
掲載誌名
International Immunology
ISSN
14602377
cat書誌ID
AA12096432
出版者
Oxford University Press|The Japanese Society for Immunology
32
2
開始ページ
117
終了ページ
131
発行日
2019-10-05
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Minoru Matsumotoの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
EDB ID
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
博士論文全文を含む
文科省報告番号
甲第3429号
学位記番号
甲医第1459号
学位授与年月日
2020-06-25
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
先端酵素学研究所