期刊
CELL REPORTS
卷 35, 期 2, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.108966
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资金
- NCI Center Core Support Grant [5P30CA016086]
- North Carolina Biotech Center Institutional Support Grant [2012-IDG-1006]
- NIH [R01AI138337, R01AI143894, R01AI131685, R21AI117575, 1R03DE027101, 1R56DE028553, R01GM10974]
- North Carolina TraCS Translational Team Science Award [TTSA004P2]
Persistent virus infections can lead to pathogenesis with weakened T cell function, while the study found that UTX enhances gene expression in CD8(+) T cells to improve CTL-mediated protection during chronic infections. However, UTX also limits the frequency and longevity of virus-specific CD8(+) T cells.
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.
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