| First Author | Zaman TS | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 6 | Pages | 1989-1997 |
| PubMed ID | 28779023 | Mgi Jnum | J:251271 |
| Mgi Id | MGI:6103675 | Doi | 10.4049/jimmunol.1700645 |
| Citation | Zaman TS, et al. (2017) Notch Balances Th17 and Induced Regulatory T Cell Functions in Dendritic Cells by Regulating Aldh1a2 Expression. J Immunol 199(6):1989-1997 |
| abstractText | 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-beta. 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. |
