Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes

DOI PDF 8 Citations
  • Silvia Cerboni
    Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France 1
  • Nadia Jeremiah
    Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France 1
  • Matteo Gentili
    Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France 1
  • Ulf Gehrmann
    Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France 1
  • Cécile Conrad
    Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France 1
  • Marie-Claude Stolzenberg
    Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France 2
  • Capucine Picard
    Center for Primary Immunodeficiencies, Hopital Necker Enfants-Malades, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France 3
  • Bénédicte Neven
    Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France 2
  • Alain Fischer
    Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France 2
  • Sébastian Amigorena
    Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France 1
  • Frédéric Rieux-Laucat
    Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France 2
  • Nicolas Manel
    Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France 1

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<jats:p>Activation of the cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is critical for IFN and inflammatory gene expression during innate immune responses. However, the role of STING in adaptive immunity is still unknown. In this study, we show that STING activation reduces the proliferation of T lymphocytes. This activity was independent of TBK1 and IRF3 recruitment and of type I IFN but required a distinct C-terminal domain of STING that activates NF-κB. Inhibition of cell proliferation by STING required its relocalization to the Golgi apparatus and caused mitotic errors. T lymphocytes from patients carrying constitutive active mutations in TMEM173 encoding STING showed impaired proliferation and reduced numbers of memory cells. Endogenous STING inhibited proliferation of mouse T lymphocytes. Therefore, STING, a critical innate sensor, also functions intrinsically in cells of the adaptive immune system to inhibit proliferation.</jats:p>

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