Signalling strength determines proapoptotic functions of STING.
- Gulen MF Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015, Lausanne, Switzerland.
- Koch U Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015, Lausanne, Switzerland.
- Haag SM Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015, Lausanne, Switzerland.
- Schuler F Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innrain 80-82, 6020, Innsbruck, Austria.
- Apetoh L INSERM U866, Faculté de Médecine, Université de Bourgogne, 7 Boulevard Jeanne d'Arc, 21078, Dijon, France.
- Villunger A Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innrain 80-82, 6020, Innsbruck, Austria.
- Radtke F Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015, Lausanne, Switzerland.
- Ablasser A Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015, Lausanne, Switzerland. andrea.ablasser@epfl.ch.
- 2017-09-07
Published in:
- Nature communications. - 2017
Animals
Apoptosis
Interferon Regulatory Factor-3
Leukemia, T-Cell
Membrane Proteins
Mice, Inbred C57BL
Protein Binding
Signal Transduction
T-Lymphocytes
Transcription, Genetic
Tumor Suppressor Protein p53
English
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1038/s41467-017-00573-w
- PMID 28874664
- Persistent URL
- https://sonar.ch/global/documents/105282
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