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Cited by 361interferon and immune responsesImmune Response and InflammationImmunotherapy and Immune Responses

Cutting Edge: Activation of STING in T Cells Induces Type I IFN Responses and Cell Death

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Larkin, Bridget, Ilyukha, Vladimir, Sorokin, Maxim, Buzdin, Anton, Vannier, Edouard, Poltorak, Alexander·2017·The Journal of Immunology
DOI 10.4049/jimmunol.1601999PMC PMC5525333
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Abstract

Stimulator of interferon genes (STING) was initially described as a sensor of intracellular bacterial and viral DNA and a promising adjuvant target in innate immune cells; more recently STING has also been shown to detect endogenous DNA and play a role in tumor immunity and autoimmune disease development. Thus far STING has been studied in macrophages and dendritic cells. In this study, to our knowledge we provide the first evidence of STING activation in T cells, in which STING agonists not only provoke type I IFN production and IFN-stimulated gene expression, mirroring the response of innate cells, but are also capable of activating cell stress and death pathways. Our results suggest a re-evaluation of STING agonist–based therapies may be necessary to identify the possible effects on the T cell compartment. Conversely, the effects of STING on T cells could potentially be harnessed for therapeutic applications.

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Crossref · 10.4049/jimmunol.1601999

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  • STING activity induces T cell apoptosis.

    “as recent evidence demonstrated that STING activity induces T cell apoptosis,85–87”

    From Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation (2023) · cites this paper as [87]

    The Results and Discussion section (“STING activation triggers T cell death”; page not provided) reports STING-dependent T-cell death in vitro and evidence implicating an apoptotic pathway. But it also suggests necroptosis can contribute and reports no T-cell death in its short-term in vivo experiment, so the unqualified claim that STING activity induces T-cell apoptosis overstates the finding. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • It was proposed that STING agonist can induce T cell death through activation of proapoptotic transcriptional programs.

    “Although it was proposed that STING agonist can induce T cell death through the activation of proapoptotic transcriptional programs58, recent studies have indicated that this effect depends on the type and doses of STING agonists59,60.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [58]

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Cites

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Research works printed but not linked: 18

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Authors
Larkin, B., Ilyukha, V., Sorokin, M., Buzdin, A., Vannier, E., & Poltorak, A.
Affiliations
  • Tufts University (US)
  • Petrozavodsk State University (RU)
  • Kurchatov Institute (RU)
  • Institute of Bioorganic Chemistry (RU)
  • Tufts Medical Center (US)
Corresponding author
  • Larkin, Bridget
  • Poltorak, Alexander
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2017-07
Volume
199
Issue
2
Pages
397-402
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.1601999
PMC
PMC5525333
OpenAlex
W2626019299
Cited by
361
References
3
Citations by year
2026: 31 · 2025: 56 · 2024: 43 · 2023: 45 · 2022: 48 · 2021: 51 · 2020: 27 · 2019: 34 · 2018: 21 · 2017: 4
FWCI
10.64
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Allergy and Infectious Diseases (T32AI007077, R21AI119833, R01AI056234, R21AI090419, R56AI056234, R21AI126050)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
STING, T cells, type I interferon, interferon-stimulated genes, STING agonist, cell death, antitumor immunity, autoimmune disease
MeSH terms
STING Protein, Animals, Immunity, Innate, Interferon Type I, Lymphocyte Activation, Macrophages, Membrane Proteins, T-Lymphocytes, Cell Death, Sequence Analysis, RNA, Mice, Endoplasmic Reticulum Stress

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