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UTX promotes CD8(+) T cell-mediated antiviral defenses but reduces T cell durability

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 by histone modifications, although it is unknown which enzymes cont...

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Detalles Bibliográficos
Autores principales: Mitchell, Joseph E., Lund, Makayla M., Starmer, Josh, Ge, Kai, Magnuson, Terry, Shpargel, Karl B., Whitmire, Jason K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112613/
https://www.ncbi.nlm.nih.gov/pubmed/33852868
http://dx.doi.org/10.1016/j.celrep.2021.108966
Descripción
Sumario: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 by histone modifications, although it is unknown which enzymes contribute to T cell loss or impaired function over time. In this study, we show that T cell receptor-stimulated CD8(+) T cells increase their expression of UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome) to enhance gene expression. During chronic lymphocytic choriomeningitis virus (LCMV) infection in mice, UTX binds to enhancers and transcription start sites of effector genes, allowing for improved cytotoxic T lymphocyte (CTL)-mediated protection, independent of its trimethylation of histone 3 lysine 27 (H3K27me3) demethylase activity. UTX also limits the frequency and durability of virus-specific CD8(+) T cells, which correspond to increased expression of inhibitory receptors. Thus, UTX guides gene expression patterns in CD8(+) T cells, advancing early antiviral defenses while reducing the longevity of CD8(+) T cell responses.