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oai:tokushima-u.repo.nii.ac.jp:02010614 2025-04-28T06:22:45Z 1713853213384:1713853295607

Development of organ-specific autoimmunity by dysregulated Aire expression Dysregulated Aire expression and autoimmunity 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 スギタ, ミズキ スギタ, ミズキ Sugita, Mizuki ウメザワ, ナツカ ウメザワ, ナツカ Umezawa, Natsuka キムラ, ナオキ キムラ, ナオキ Kimura, Naoki ササキ, ヒロカズ ササキ, ヒロカズ Sasaki, Hirokazu 河野, 弘 カワノ, ヒロシ Kawano, Hiroshi 河野 カワノ Kawano 弘 ヒロシ Hiroshi 70274199 西岡, 安彦 ニシオカ, ヤスヒコ Nishioka, Yasuhiko 西岡 ニシオカ Nishioka 安彦 ヤスヒコ Yasuhiko 松本, 穣 マツモト, ミノル Matsumoto, Minoru 松本 マツモト Matsumoto 穣 ミノル Minoru 尾矢, 剛志 オヤ, タケシ Oya, Takeshi 尾矢 オヤ Oya 剛志 タケシ Takeshi 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 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 open access This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Aire autoimmune disease EAE mTEC polymyositis self-tolerance Deficiency for AIRE/Aire in both humans and mice results in the development of organ-specific autoimmune disease. We tested whether augmented and/or dysregulated AIRE/Aire expression might be also prone to the breakdown of self-tolerance. To define the effect of augmented Aire expression on the development of autoimmunity, antigen-specific clonal deletion and production of clonotypic regulatory T cells (Tregs) in the thymus were examined using mice expressing two additional copies of Aire in a heterozygous state (3xAire-knockin mice: 3xAire-KI). We found that both clonal deletion of autoreactive T cells and production of clonotypic Tregs in the thymus from 3xAire-KI were impaired in a T-cell receptor-transgenic system. Furthermore, 3xAire-KI females showed higher scores of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein than wild-type littermates, suggesting that augmented Aire expression exacerbates organ-specific autoimmunity under disease-prone conditions. In humans, we found that one patient with amyopathic dermatomyositis showed CD3–CD19– cells expressing AIRE in the peripheral blood before the treatment but not during the remission phase treated with immunosuppressive drugs. Thus, not only loss of function of AIRE/Aire but also augmented and/or dysregulated expression of AIRE/Aire should be considered for the pathogenesis of organ-specific autoimmunity. We suggest that further analyses should be pursued to establish a novel link between organ-specific autoimmune disease and dysregulated AIRE expression in clinical settings. Australian and New Zealand Society for Immunology Wiley 2022-03-21 eng journal article VoR 387313 https://tokushima-u.repo.nii.ac.jp/records/2010614 https://doi.org/10.1111/imcb.12546 10.1111/imcb.12546 14401711 AA10678685 Immunology & Cell Biology 100 5 371 377 https://tokushima-u.repo.nii.ac.jp/record/2010614/files/icb_100_5_371.pdf application/pdf 781 KB 2023-01-31