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- Title
Notch activation on effector T cells increases their sensitivity to Treg cell-mediated suppression through upregulation of TGF-β RII expression.
- Authors
Hue, Sophie; Kared, Hassen; Mehwish, Younas; Mouhamad, Shahul; Balbo, Michelle; Levy, Yves
- Abstract
Notch proteins play an important role in embryonic development and cell-fate decisions. Notch influences also the activation and differentiation of peripheral T cells. Here, we investigated whether Notch signaling modulates the response of effector T cells to regulatory T ( Treg) cells. Pre-exposure of CD4+ CD25− effector T cells to the Notch ligands Delta-4 and Jagged-1, but not Delta-1, increases significantly effector T-cell sensitivity to Treg cell-mediated suppression through upregulation of TGF-β RII expression and increased levels of the phosphorylated form of the Smad 3 protein. This effect is relieved by anti- TGF-β Abs. We demonstrate that HES (hairy and enhancer of split), the main transcription factor downstream of Notch, induces strong transactivation of TGF-ß RII by binding the TGF-β RII promoter through its DNA-binding domain. Thus, the crosstalk between Notch and the TGF-β pathway leads to potentiation of the suppressive effect of Treg cells.
- Publication
European Journal of Immunology, 2012, Vol 42, Issue 7, p1796
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201142330