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

Sophie Hue 1, 2 Hassen Kared 1 Younas Mehwish 1 Shahul Mouhamad 1 Michelle Balbo 1 Yves Levy 1, 3, *
* Auteur correspondant
1 IMRB - Institut Mondor de Recherche Biomédicale
2 Service d'immunologie biologique
3 Service d'immunologie clinique [Créteil]
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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European Journal of Immunology, Wiley-VCH Verlag, 2012, 42 (7), pp.1796-803. 〈10.1002/eji.201142330〉
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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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