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

DOI IR NDL Digital Collections

Bibliographic Information

Title
Notch Balances Th17 and Induced Regulatory T Cell Functions in Dendritic Cells by Regulating Aldh1a2 Expression
Other 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
Author
Zaman, Taskia Sultana
Alias Name
  • ザマン, タスキア サルタナ
  • ザマン, タスキア サルタナ
Author
Arimochi, Hideki
Alias Name
  • 有持, 秀喜
  • アリモチ, ヒデキ
Author
Maruyama, Satoshi
Alias Name
  • マルヤマ, サトシ
  • マルヤマ, サトシ
Author
Ishifune, Chieko
Alias Name
  • 石舟, 智恵子
  • イシフネ, チエコ
Author
Tsukumo, Shin-ichi
Alias Name
  • 九十九, 伸一
  • ツクモ, シンイチ
Author
Kitamura, Akiko
Alias Name
  • 北村, 明子
  • キタムラ, アキコ
Author
Yasutomo, Koji
Alias Name
  • 安友, 康二
  • ヤストモ, コウジ
University
徳島大学
Types of degree
博士（医学）
Grant ID
甲医第1344号
Degree year
2017-09-28

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 (Rbpj−/− 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-β. 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 Rbpj−/− 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 Rbpj−/− mice improved colitis compared with transfer of naive CD4+ T cell alone. Furthermore, cotransfer of DCs from Rbpj−/− mice that overexpressed Aldh1a2 or Notch-stimulated DCs together with naive CD4+ T cells into Rbpj−/− 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.

Keywords

Details 詳細情報について

Report a problem

Back to top