RELA tunes innate-like interferon I/III responses in human T cells.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
01 05 2023
01 05 2023
Historique:
received:
15
04
2022
revised:
11
11
2022
accepted:
10
01
2023
entrez:
23
2
2023
pubmed:
24
2
2023
medline:
3
3
2023
Statut:
ppublish
Résumé
In innate immune cells, intracellular sensors such as cGAS-STING stimulate type I/III interferon (IFN) expression, which promotes antiviral defense and immune activation. However, how IFN-I/III expression is controlled in adaptive cells is poorly understood. Here, we identify a transcriptional rheostat orchestrated by RELA that confers human T cells with innate-like abilities to produce IFN-I/III. Despite intact cGAS-STING signaling, IFN-I/III responses are stunted in CD4+ T cells compared with dendritic cells or macrophages. We find that lysine residues in RELA tune the IFN-I/III response at baseline and in response to STING stimulation in CD4+ T cells. This response requires positive feedback driven by cGAS and IRF7 expression. By combining RELA with IRF3 and DNA demethylation, IFN-I/III production in CD4+ T cells reaches levels observed in dendritic cells. IFN-I/III production provides self-protection of CD4+ T cells against HIV infection and enhances the elimination of tumor cells by CAR T cells. Therefore, innate-like functions can be tuned and leveraged in human T cells.
Identifiants
pubmed: 36820829
pii: 213889
doi: 10.1084/jem.20220666
pmc: PMC9998965
pii:
doi:
Substances chimiques
Nucleotidyltransferases
EC 2.7.7.-
Interferon Type I
0
RELA protein, human
0
Transcription Factor RelA
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Jeremiah et al.
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