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UTX constrains antiviral CD8+ T cell responses during chronic virus infection

ABSTRACT: Persistent virus infections can cause pathogenesis that is debilitating or lethal. During these infections, virus-specific T cells fail to protect due to weakened antiviral activity or failure to persist. These outcomes are governed epigenetically, though it is unknown which enzymes contribute to T cell loss or impaired function over time. Here, we show that T cell receptor-stimulated CD8+ T cells increase their expression of UTX (Ubiquitously transcribed Tetratricopeptide repeat, X-chromosome), an enzyme involved in demethylating histone-3 lysine-27 (H3K27), and reduce genome-wide H3K27-me3. UTX limits the frequency and durability of virus-specific CD8+ T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice by promoting inhibitory receptor expression and apoptosis. UTX also increases effector gene expression to improve CTL-mediated protection, a process corresponding to reduced H3K27me3 at effector gene bodies. Thus, UTX guides gene expression patterns in CD8+ T cells, promoting antiviral activity while reducing CD8+ T cell durability.

ORGANISM(S): Mus musculus

PROVIDER: GSE143736 | GEO | 2021/02/09

REPOSITORIES: GEO

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UTX constrains antiviral CD8+ T cell responses during chronic virus infection

Project description:UTX constrains antiviral CD8+ T cell responses during chronic virus infection

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