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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
Author
Zaman, Taskia Sultana Tokushima University
Maruyama, Satoshi Tokushima University
Keywords
Notch
dendritic cells
Aldh1a2
Th17
iTreg
Content Type
Thesis or Dissertation
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.
Journal Title
The Journal of Immunology
ISSN
00221767
15506606
NCID
AA12530845
AA00699656
Publisher
The American Association of Immunologists
Volume
199
Issue
6
Start Page
1989
End Page
1997
Published Date
2017-09-05
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
TextVersion
ETD
MEXT report number
甲第3100号
Diploma Number
甲医第1344号
Granted Date
2017-09-28
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences