Signalling strength determines proapoptotic functions of STING

Nat Commun. 2017 Sep 5;8(1):427. doi: 10.1038/s41467-017-00573-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Interferon Regulatory Factor-3 / metabolism
  • Leukemia, T-Cell / immunology
  • Leukemia, T-Cell / pathology
  • Membrane Proteins / metabolism*
  • Mice, Inbred C57BL
  • Protein Binding
  • Signal Transduction*
  • T-Lymphocytes / metabolism
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • MPYS protein, mouse
  • Membrane Proteins
  • Tumor Suppressor Protein p53