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Notch activation on effector T cells increases their sensitivity to Treg cell-mediated suppression through upregulation of TGF-βRII expression.

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-βRII 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-ßRII by binding the TGF-βRII 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.
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https://www.hal.inserm.fr/inserm-00727385
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Submitted on : Monday, September 3, 2012 - 3:18:36 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:42 AM
Long-term archiving on: : Tuesday, December 4, 2012 - 3:41:45 AM

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Sophie Hue, Hassen Kared, Younas Mehwish, Shahul Mouhamad, Michelle Balbo, et al.. Notch activation on effector T cells increases their sensitivity to Treg cell-mediated suppression through upregulation of TGF-βRII expression.. European Journal of Immunology, Wiley-VCH Verlag, 2012, 42 (7), pp.1796-803. ⟨10.1002/eji.201142330⟩. ⟨inserm-00727385⟩

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