Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms

• Material Type: 博士論文
• Title: Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms
• Author/Editor: Matsumoto, Minoru; Tsuneyama, Koichi; Morimoto, Junko; Hosomichi, Kazuyoshi; Matsumoto, Mitsuru; Nishijima, Hitoshi
• Author Heading: Matsumoto, Minoru; Tsuneyama, Koichi; Morimoto, Junko; Hosomichi, Kazuyoshi; Matsumoto, Mitsuru; Nishijima, Hitoshi
• Publication, Distribution, etc.: Oxford University Press|The Japanese Society for Immunology
• Publication Date: 2019-10-05
• Publication Date (W3CDTF): 2019-10-05
• Alternative Title: 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
• Periodical title: International Immunology
• No. or year of volume/issue: 32 2
• Volume: 32
• Issue: 2
• Pages: 117-131
• ISSN (Periodical Title): ISSN : 1460-2377
• Degree grantor/type: 徳島大学
• Date Granted: 2020-06-25
• Dissertation Number: 甲第3429号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Aire; 1型糖尿病; Xcr1陽性樹状細胞; NOD; mTEC; type 1 diabetes; Xcr1+ DC
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): 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 [e-mail]
• Related Material (DOI): 10.1093/intimm/dxz066
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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