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

• Material Type: 博士論文
• Title: Notch Balances Th17 and Induced Regulatory T Cell Functions in Dendritic Cells by Regulating Aldh1a2 Expression
• 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
• No. or year of volume/issue: 199 6
• Volume: 199
• Issue: 6
• Pages: 1989-1997
• ISSN (Periodical Title): ISSN : 0022-1767; ISSN : 1550-6606
• Degree grantor/type: 徳島大学
• Date Granted: 2017-09-28
• Dissertation Number: 甲第3100号
• Degree Type: 博士（医学）
• 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.4049/jimmunol.1700645
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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