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Signalling strength determines proapoptotic functions of STING

Author

Listed:
  • Muhammet F. Gulen

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Ute Koch

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Simone M. Haag

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Fabian Schuler

    (Medical University of Innsbruck)

  • Lionel Apetoh

    (Université de Bourgogne)

  • Andreas Villunger

    (Medical University of Innsbruck
    Tyrolean Cancer Research Institute)

  • Freddy Radtke

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Andrea Ablasser

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

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.

Suggested Citation

  • Muhammet F. Gulen & Ute Koch & Simone M. Haag & Fabian Schuler & Lionel Apetoh & Andreas Villunger & Freddy Radtke & Andrea Ablasser, 2017. "Signalling strength determines proapoptotic functions of STING," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00573-w
    DOI: 10.1038/s41467-017-00573-w
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    Cited by:

    1. Jeremy J. Ratiu & William E. Barclay & Elliot Lin & Qun Wang & Sebastian Wellford & Naren Mehta & Melissa J. Harnois & Devon DiPalma & Sumedha Roy & Alejandra V. Contreras & Mari L. Shinohara & David , 2022. "Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Matteo Gentili & Bingxu Liu & Malvina Papanastasiou & Deborah Dele-Oni & Marc A. Schwartz & Rebecca J. Carlson & Aziz M. Al’Khafaji & Karsten Krug & Adam Brown & John G. Doench & Steven A. Carr & Nir , 2023. "ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    3. Chiara Scopa & Samantha M. Barnada & Maria E. Cicardi & Mo Singer & Davide Trotti & Marco Trizzino, 2023. "JUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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