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RELA tunes innate-like interferon I/III responses in human T cells.

ABSTRACT: 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.

SUBMITTER: Jeremiah N

PROVIDER: S-EPMC9998965 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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RELA tunes innate-like interferon I/III responses in human T cells.

Jeremiah Nadia N Ferran Hermine H Antoniadou Konstantina K De Azevedo Kevin K Nikolic Jovan J Maurin Mathieu M Benaroch Philippe P Manel Nicolas N

The Journal of experimental medicine 20230223 5

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 ...[more]

PMID: 36820829

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Dataset Information

RELA tunes innate-like interferon I/III responses in human T cells.

Publications

RELA tunes innate-like interferon I/III responses in human T cells.

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