UTX promotes CD8+ T cell-mediated antiviral defenses but reduces T cell durability.
Cell Rep
; 35(2): 108966, 2021 04 13.
Article
en En
| MEDLINE
| ID: mdl-33852868
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 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
/
Citotoxicidad Inmunológica
/
Histona Demetilasas
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Memoria Inmunológica
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Coriomeningitis Linfocítica
/
Virus de la Coriomeningitis Linfocítica
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos