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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.
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01623390
Contributeur : Lnc - Université de Bourgogne Connectez-vous pour contacter le contributeur
Soumis le : mercredi 25 octobre 2017 - 11:35:36
Dernière modification le : vendredi 8 juin 2018 - 14:50:25
Contributeur : Lnc - Université de Bourgogne Connectez-vous pour contacter le contributeur
Soumis le : mercredi 25 octobre 2017 - 11:35:36
Dernière modification le : vendredi 8 juin 2018 - 14:50:25
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