Notch Balances Th17 and Induced Regulatory T Cell Functions in Dendritic Cells by Regulating Aldh1a2 Expression

• Material Type: 博士論文
• ISSN: 0022-1767
• Title: Notch Balances Th17 and Induced Regulatory T Cell Functions in Dendritic Cells by Regulating Aldh1a2 Expression
• Volume: 199 6
• Author/Editor: Zaman, Taskia Sultana; Arimochi, Hideki; Maruyama, Satoshi; Ishifune, Chieko; Tsukumo, Shin-ichi; Kitamura, Akiko; Yasutomo, Koji
• Author Heading: Zaman, Taskia Sultana; Arimochi, Hideki; Maruyama, Satoshi; Ishifune, Chieko; Tsukumo, Shin-ichi; Kitamura, Akiko; Yasutomo, Koji
• Publication, Distribution, etc.: The American Association of Immunologists
• Publication Date: 2017-09-05
• Publication Date (W3CDTF): 2017-09-05
• Alternative Title: NotchタンパクはAldh1a2遺伝子の発現を調整することで、樹状細胞のTh17細胞誘導と誘導性制御性T細胞誘導の平衡を保っている; Notch AND Aldh1a2 REGULATION IN DCs
• Periodical title: The Journal of Immunology
• Degree grantor/type: 徳島大学
• Date Granted: 2017-09-28
• Date Granted (W3CDTF): 2017-09-28
• Dissertation Number: 甲第3100号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3100号
• Text Language Code: eng
• Subject Heading: Notch; dendritic cells; Aldh1a2; Th17; iTreg
• Target Audience: 一般
• Note (General): Dendritic cells (DCs) are important for adaptive immune responses through the activation of T cells. The molecular interplay between DCs and T cells determines the magnitude of T cell responses or outcomes of functional differentiation of T cells. In this study, we demonstrated that DCs in mice that are Rbpj deficient in CD11c+ cells (Rbpj2/2 mice) promoted the differentiation of IL-17A–producing Th17 cells. Rbpj-deficient DCs expressed little Aldh1a2 protein that is required for generating retinoic acid. Those DCs exhibited a reduced ability for differentiating regulatory T cells induced by TGF-b. Rbpj protein directly regulated Aldh1a2 transcription by binding to its promoter region. The overexpression of Aldh1a2 in Rbpj-deficient DCs negated their Th17-promoting ability. Transfer of naive CD4+ T cells into Rag1-deficient Rbpj2/2 mice enhanced colitis with increased Th17 and reduced induced regulatory T cells (iTreg) compared with control Rag1-deficient mice. The cotransfer of iTreg and naive CD4+ T cells into Rag1-deficient Rbpj2/2 mice improved colitis compared with transfer of naive CD4+ T cell alone. Furthermore, cotransfer of DCs from Rbpj2/2 mice that overexpressed Aldh1a2 or Notch-stimulated DCs together with naive CD4+ T cells into Rbpj2/2 Rag1-deficient mice led to reduced colitis with increased iTreg numbers. Therefore, our studies identify Notch signaling in DCs as a crucial balancer of Th17/iTreg, which depends on the direct regulation of Aldh1a2 transcription in DCs.
• DOI: info:doi/10.4049/jimmunol.1700645; https://doi.org/info:doi/10.4049/jimmunol.1700645
• Persistent ID (NDL): info:ndljp/pid/11008883; https://dl.ndl.go.jp/pid/11008883
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• 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): 2018-01-02T17:18:43+09:00
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• Periodical Title (URI): https://repo.lib.tokushima-u.ac.jp/110921
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