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ID 106133
タイトル別表記
Rbpjの欠損はCD4陽性T細胞によるIL-22産生を抑制することで実験的自己免疫性網膜ブドウ膜炎の症状を軽減させる
Abrogation of Rbpj attenuates uveoretinitis
著者
ブヤ, ザイド アハマド 徳島大学大学院医科学教育部(医学専攻)
Asanoma, Michihito The University of Tokushima
岩田, 明子 The University of Tokushima
Maekawa, Yoichi The University of Tokushima
キーワード
Notch
Rbpj
EAU (Experimental Autoimmune Uveoretinitis)
GSI (γ secretase inhibitor)
IL-22
資料タイプ
学位論文
抄録
Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated disease induced by immunizing mice with interphotoreceptor retinoid binding protein (IRBP). Autoaggressive CD4+ T cells are the major pathogenic population for EAU. We investigated the contribution of Notch signaling in T cells to EAU pathogenesis because Notch signaling regulates various aspects of CD4+ T cell functions. Rbpj is required for Notch signaling, and Rbpj deficiency in T cells inhibited EAU disease severity. The amelioration of EAU in T cell-specific Rbpj-deficient mice correlated with low levels of IL-22 production from CD4+ T cells, although IRBP-specific CD4+ T cell proliferation and Th17 differentiation were unaffected. Administration of recombinant IL-22 during the late phase, but not the early phase, of EAU increased EAU clinical scores in T cell-specific Rbpj-deficient mice. Notch inhibition in mice immunized with IRBP with a γ-secretase inhibitor (GSI) suppressed EAU progression, even when GSI was administered as late as 13 days after IRBP immunization. Our data demonstrate that Rbpj/Notch-mediated IL-22 production in T cells has a key pathological role in the late phase of EAU, and suggest that Notch blockade might be a useful therapeutic approach for treating EAU.
掲載誌名
PLOS ONE
ISSN
19326203
出版者
PLOS
9
2
開始ページ
e89266
発行日
2014-02-28
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201405131004.pdf
論文本文 : LID201405281002.pdf
本論文は, 著者Zaied Ahmed Bhuyanの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
©2014 Bhuyan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.( https://creativecommons.org/licenses/by/4.0/ )
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2740号
学位記番号
甲医第1201号
学位授与年月日
2014-03-19
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系