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

European Journal of Immunology
Sophie HueYves Levy

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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Citations

Dec 11, 2013·Clinical & Developmental Immunology·Ribal BassilWassim Elyaman
Mar 30, 2016·Immunology and Cell Biology·Tamara Tilburgs, Jack L Strominger
Dec 25, 2013·Circulation Journal : Official Journal of the Japanese Circulation Society·Antonio D LassalettaFrank W Sellke
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Nov 5, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Catarina MotaIris Caramalho
Aug 13, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Subhasis BarikHabib Zaghouani
Sep 11, 2020·Scientific Reports·Susana López-LópezMaría José M Díaz-Guerra

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