| First Author | Mitchell JE | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 2 | Pages | 108966 |
| PubMed ID | 33852868 | Mgi Jnum | J:324671 |
| Mgi Id | MGI:6716776 | Doi | 10.1016/j.celrep.2021.108966 |
| Citation | Mitchell JE, et al. (2021) UTX promotes CD8(+) T cell-mediated antiviral defenses but reduces T cell durability. Cell Rep 35(2):108966 |
| abstractText | 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. |
