| First Author | Zebley CC | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 2 | Pages | 109796 |
| PubMed ID | 34644568 | Mgi Jnum | J:324665 |
| Mgi Id | MGI:6881809 | Doi | 10.1016/j.celrep.2021.109796 |
| Citation | Zebley CC, et al. (2021) Proinflammatory cytokines promote TET2-mediated DNA demethylation during CD8 T cell effector differentiation. Cell Rep 37(2):109796 |
| abstractText | To gain insight into the signaling determinants of effector-associated DNA methylation programming among CD8 T cells, we explore the role of interleukin (IL)-12 in the imprinting of IFNg expression during CD8 T cell priming. We observe that anti-CD3/CD28-mediated stimulation of human naive CD8 T cells is not sufficient to induce substantial demethylation of the IFNg promoter. However, anti-CD3/CD28 stimulation in the presence of the inflammatory cytokine, IL-12, results in stable demethylation of the IFNg locus that is commensurate with IFNg expression. IL-12-associated demethylation of the IFNg locus is coupled to cell division through TET2-dependent demethylation in an ex vivo human chimeric antigen receptor T cell model system and an in vivo immunologically competent murine system. Collectively, these data illustrate that IL-12 signaling promotes TET2-mediated effector DNA demethylation programming in CD8 T cells and serve as proof of concept that cytokines can guide induction of epigenetically regulated traits for T cell-based immunotherapies. |
