ID | 110921 |
Title Alternative | 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
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Author |
Zaman, Taskia Sultana
Tokushima University
Arimochi, Hideki
Tokushima University
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Maruyama, Satoshi
Tokushima University
Ishifune, Chieko
Tokushima University
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Tsukumo, Shin-ichi
Tokushima University
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Yasutomo, Koji
Tokushima University
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Keywords | Notch
dendritic cells
Aldh1a2
Th17
iTreg
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Content Type |
Thesis or Dissertation
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Description | 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.
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Journal Title |
The Journal of Immunology
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ISSN | 00221767
15506606
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NCID | AA12530845
AA00699656
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Publisher | The American Association of Immunologists
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Volume | 199
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Issue | 6
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Start Page | 1989
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End Page | 1997
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Published Date | 2017-09-05
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Remark | 内容要旨・審査要旨・論文本文の公開
本論文は, 著者Taskia Sultana Zaman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。 |
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3100号
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Diploma Number | 甲医第1344号
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Granted Date | 2017-09-28
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
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