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J Exp Med. 2017 Jun 5;214(6):1769-1785. doi: 10.1084/jem.20161674. Epub 2017 May 8.

Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes.

Author information

1
Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France.
2
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.
3
Center for Primary Immunodeficiencies, Hopital Necker Enfants-Malades, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
4
Pediatric Immunology, Hematology, and Rheumatology Unit, Hopital Necker Enfants-Malades, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
5
Collège de France, 75005 Paris, France.
6
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 nicolas.manel@curie.fr frederic.rieux-laucat@inserm.fr.
7
Immunity and Cancer Department, Institut Curie, PSL Research University, Institut National de la Santé et de la Recherche Médicale U932, 75005 Paris, France nicolas.manel@curie.fr frederic.rieux-laucat@inserm.fr.

Abstract

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.

PMID:
28484079
PMCID:
PMC5461003
DOI:
10.1084/jem.20161674
[Indexed for MEDLINE]
Free PMC Article

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