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

• Material Type: 博士論文
• ISSN: 1460-2377
• Title: Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms
• Volume: 32 2
• 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
• Degree grantor/type: 徳島大学
• Date Granted: 2020-06-25
• Date Granted (W3CDTF): 2020-06-25
• Dissertation Number: 甲第3429号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3429号
• 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.
• DOI: info:doi/10.1093/intimm/dxz066; https://doi.org/info:doi/10.1093/intimm/dxz066
• Persistent ID (NDL): info:ndljp/pid/11526014; https://dl.ndl.go.jp/pid/11526014
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-08-11T22:41:34+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/114944
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp