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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.

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