| First Author | Yamada T | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 4 | Pages | 1088-1098 |
| PubMed ID | 30626691 | Mgi Jnum | J:272978 |
| Mgi Id | MGI:6280836 | Doi | 10.4049/jimmunol.1801083 |
| Citation | Yamada T, et al. (2019) Histone H3K27 Demethylase Negatively Controls the Memory Formation of Antigen-Stimulated CD8(+) T Cells. J Immunol 202(4):1088-1098 |
| abstractText | Although the methylation status of histone H3K27 plays a critical role in CD4(+) T cell differentiation and its function, the role of Utx histone H3K27 demethylase in the CD8(+) T cell-dependent immune response remains unclear. We therefore generated T cell-specific Utx (flox/flox) Cd4-Cre Tg (Utx KO) mice to determine the role of Utx in CD8(+) T cells. Wild-type (WT) and Utx KO mice were infected with Listeria monocytogenes expressing OVA to analyze the immune response of Ag-specific CD8(+) T cells. There was no significant difference in the number of Ag-specific CD8(+) T cells upon primary infection between WT and Utx KO mice. However, Utx deficiency resulted in more Ag-specific CD8(+) T cells upon secondary infection. Adoptive transfer of Utx KO CD8(+) T cells resulted in a larger number of memory cells in the primary response than in WT. We observed a decreased gene expression of effector-associated transcription factors, including Prdm1 encoding Blimp1, in Utx KO CD8(+) T cells. We confirmed that the trimethylation level of histone H3K27 in the Prdm1 gene loci in the Utx KO cells was higher than in the WT cells. The treatment of CD8(+) T cells with Utx-cofactor alpha-ketoglutarate hampered the memory formation, whereas Utx inhibitor GSK-J4 enhanced the memory formation in WT CD8(+) T cells. These data suggest that Utx negatively controls the memory formation of Ag-stimulated CD8(+) T cells by epigenetically regulating the gene expression. Based on these findings, we identified a critical link between Utx and the differentiation of Ag-stimulated CD8(+) T cells. |
