Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice

Shino Niki, Kiyotaka Oshikawa, Yasuhiro Mouri, Fumiko Hirota, Akemi Matsushima, Masashi Yano, Hongwei Han, Yoshimi Bando, Keisuke Izumi, Masaki Matsumoto, Keiichi I. Nakayama, Noriyuki Kuroda, Mitsuru Matsumoto

研究成果: ジャーナルへの寄稿記事

77 引用 (Scopus)

抄録

Factors that determine the spectrum of target organs involved in autoimmune destruction are poorly understood. Although loss of function of autoimmune regulator (AIRE) in thymic epithelial cells is responsible for autoimmunity, the pathogenic roles of AIRE in regulating target-organ specificity remain elusive. In order to gain insight into this issue, we have established NOD mice, an animal model of type 1 diabetes caused by autoimmune attack against β cell islets, in which Aire has been abrogated. Remarkably, acinar cells rather than β cell islets were the major targets of autoimmune destruction in Aire-deficient NOD mice, and this alteration of intra-pancreatic target-organ specificity was associated with production of autoantibody against pancreas-specific protein disulfide isomerase (PDIp), an antigen expressed predominantly by acinar cells. Consistent with this pathological change, the animals were resistant to the development of diabetes. The results suggest that Aire not only is critical for the control of self-tolerance but is also a strong modifier of target-organ specificity through regulation of T cell repertoire diversification. We also demonstrated that transcriptional expression of PDIp was retained in the Aire-deficient NOD thymus, further supporting the concept that Aire may regulate the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus.

元の言語英語
ページ(範囲)1292-1301
ページ数10
ジャーナルJournal of Clinical Investigation
116
発行部数5
DOI
出版物ステータス出版済み - 5 1 2006

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Organ Specificity
Inbred NOD Mouse
Acinar Cells
Islets of Langerhans
Thymus Gland
Protein Disulfide-Isomerases
T-Lymphocytes
Self Tolerance
Autoimmunity
Type 1 Diabetes Mellitus
Autoantibodies
Pancreas
Animal Models
Epithelial Cells
Antigens
Proteins

All Science Journal Classification (ASJC) codes

  • Medicine(all)

これを引用

Niki, S., Oshikawa, K., Mouri, Y., Hirota, F., Matsushima, A., Yano, M., ... Matsumoto, M. (2006). Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice. Journal of Clinical Investigation, 116(5), 1292-1301. https://doi.org/10.1172/JCI26971

Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice. / Niki, Shino; Oshikawa, Kiyotaka; Mouri, Yasuhiro; Hirota, Fumiko; Matsushima, Akemi; Yano, Masashi; Han, Hongwei; Bando, Yoshimi; Izumi, Keisuke; Matsumoto, Masaki; Nakayama, Keiichi I.; Kuroda, Noriyuki; Matsumoto, Mitsuru.

:: Journal of Clinical Investigation, 巻 116, 番号 5, 01.05.2006, p. 1292-1301.

研究成果: ジャーナルへの寄稿記事

Niki, S, Oshikawa, K, Mouri, Y, Hirota, F, Matsushima, A, Yano, M, Han, H, Bando, Y, Izumi, K, Matsumoto, M, Nakayama, KI, Kuroda, N & Matsumoto, M 2006, 'Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice', Journal of Clinical Investigation, 巻. 116, 番号 5, pp. 1292-1301. https://doi.org/10.1172/JCI26971
Niki, Shino ; Oshikawa, Kiyotaka ; Mouri, Yasuhiro ; Hirota, Fumiko ; Matsushima, Akemi ; Yano, Masashi ; Han, Hongwei ; Bando, Yoshimi ; Izumi, Keisuke ; Matsumoto, Masaki ; Nakayama, Keiichi I. ; Kuroda, Noriyuki ; Matsumoto, Mitsuru. / Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice. :: Journal of Clinical Investigation. 2006 ; 巻 116, 番号 5. pp. 1292-1301.
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AU - Matsushima, Akemi

AU - Yano, Masashi

AU - Han, Hongwei

AU - Bando, Yoshimi

AU - Izumi, Keisuke

AU - Matsumoto, Masaki

AU - Nakayama, Keiichi I.

AU - Kuroda, Noriyuki

AU - Matsumoto, Mitsuru

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