Affiliation:
1. Institut Curie 1 , Paris, France
2. , Paris Sciences et Lettres Research University, INSERM U932 1 , Paris, France
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.
Funder
Institut National de la Santé et de la Recherche Médicale
Institut Curie
Agence Nationale de la Recherche
Fondation pour la Recherche Médicale
Agence Nationale de Recherches sur le Sida et les Hépatites Virales
Région Ile-de-France
Sidaction
Fondation Chercher et Trouver
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
7 articles.
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