2026-03-05T07:12:50Z https://tokushima-u.repo.nii.ac.jp/oai

oai:tokushima-u.repo.nii.ac.jp:02007876 2025-04-28T07:15:17Z 1713853213384:1713853296295:1716267876683:1716268551628

Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms 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 松本, 穣 マツモト, ミノル Matsumoto, Minoru 松本 マツモト Matsumoto 穣 ミノル Minoru 10293341 常山, 幸一 ツネヤマ, コウイチ Tsuneyama, Koichi 常山 ツネヤマ Tsuneyama 幸一 コウイチ Koichi 20451396 森本, 純子 モリモト, ジュンコ Morimoto, Junko 森本 モリモト Morimoto 純子 ジュンコ Junko ホソミチ, カズヨシ ホソミチ, カズヨシ Hosomichi, Kazuyoshi 60221595 松本, 満 マツモト, ミツル Matsumoto, Mitsuru 松本 マツモト Matsumoto 満 ミツル Mitsuru 60425410 西嶋, 仁 ニシジマ, ヒトシ Nishijima, Hitoshi 西嶋 ニシジマ Nishijima 仁 ヒトシ Hitoshi open access This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, 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 Aire 1型糖尿病 Xcr1陽性樹状細胞 NOD mTEC type 1 diabetes Xcr1+ DC 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. Oxford University Press The Japanese Society for Immunology 2019-10-05 eng doctoral thesis NA 363244 https://tokushima-u.repo.nii.ac.jp/records/2007876 https://doi.org/10.1093/intimm/dxz066 10.1093/intimm/dxz066 14602377 AA12096432 International Immunology 32 2 117 131 甲医第1459号 博士（医学） 2020-06-25 徳島大学 https://tokushima-u.repo.nii.ac.jp/record/2007876/files/k3429_abstract_review.pdf application/pdf 209 KB 2020-07-07 https://tokushima-u.repo.nii.ac.jp/record/2007876/files/k3429_fulltext.pdf application/pdf 5.53 MB 2020-07-07