STING agonism turns human T cells into interferon-producing cells but impedes their functionality.
STING
T cell
T cell dysfunction
antiviral immune response
cGAS
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 03 2023
06 03 2023
Historique:
revised:
05
01
2023
received:
03
06
2022
accepted:
09
01
2023
pubmed:
28
1
2023
medline:
8
3
2023
entrez:
27
1
2023
Statut:
ppublish
Résumé
The cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) axis is the predominant DNA sensing system in cells of the innate immune system. However, human T cells also express high levels of STING, while its role and physiological trigger remain largely unknown. Here, we show that the cGAS-STING pathway is indeed functional in human primary T cells. In the presence of a TCR-engaging signal, both cGAS and STING activation switches T cells into type I interferon-producing cells. However, T cell function is severely compromised following STING activation, as evidenced by increased cell death, decreased proliferation, and impaired metabolism. Interestingly, these different phenotypes bifurcate at the level of STING. While antiviral immunity and cell death require the transcription factor interferon regulatory factor 3 (IRF3), decreased proliferation is mediated by STING independently of IRF3. In summary, we demonstrate that human T cells possess a functional cGAS-STING signaling pathway that can contribute to antiviral immunity. However, regardless of its potential antiviral role, the activation of the cGAS-STING pathway negatively affects T cell function at multiple levels. Taken together, these results could help inform the future development of cGAS-STING-targeted immunotherapies.
Identifiants
pubmed: 36705069
doi: 10.15252/embr.202255536
pmc: PMC9986811
doi:
Substances chimiques
Nucleotidyltransferases
EC 2.7.7.-
Interferon Type I
0
Antiviral Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e55536Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : SFB TRR 338
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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