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Signalling strength determines proapoptotic functions of STING

Abstract : Mammalian cells use cytosolic nucleic acid receptors to detect pathogens and other stress signals. In innate immune cells the presence of cytosolic DNA is sensed by the cGAS-STING signalling pathway, which initiates a gene expression programme linked to cellular activation and cytokine production. Whether the outcome of the STING response varies between distinct cell types remains largely unknown. Here we show that T cells exhibit an intensified STING response, which leads to the expression of a distinct set of genes and results in the induction of apoptosis. Of note, this proapoptotic STING response is still functional in cancerous T cells and delivery of small molecule STING agonists prevents in vivo growth of T-cell-derived tumours independent of its adjuvant activity. Our results demonstrate how the magnitude of STING signalling can shape distinct effector responses, which may permit for cell type-adjusted behaviours towards endogenous or exogenous insults.The cGAS/STING signalling pathway is responsible for sensing intracellular DNA and activating downstream inflammatory genes. Here the authors show mouse primary T cells and T leukaemia are hyperresponsive to STING agonist, and this strong STING signalling is associated with apoptosis induction.
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Soumis le : mercredi 25 octobre 2017 - 11:35:36
Dernière modification le : dimanche 26 juin 2022 - 01:54:43

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Muhammet F. Gulen, Ute Koch, Simone M Haag, Fabian Schuler, Lionel Apetoh, et al.. Signalling strength determines proapoptotic functions of STING. Nature Communications, 2017, 8 (1), pp.427. ⟨10.1038/s41467-017-00573-w⟩. ⟨hal-01623390⟩



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