IL-12 Signaling Promotes TET2-Mediated DNA Demethylation During CD8 T Cell Effector Differentiation

• DOI: 10.2139/ssrn.3720007
• Publication Date: 2020-11-04T03:02:24Z
• Authors: Caitlin C. Zebley; Hossam A. Abdelsamed; Hazem E. Ghoneim; Shanta Alli; Dalia Haydar; Tarsha Harris; Maureen A. McGargill; Giedre Krenciute; Ben Youngblood
• Keywords: DNA demethylation; Demethylation

CD8 T cell memory differentiation endows cells with an ability to rapidly induce effector functions upon pathogen re-encounter. While it is well established that substantial epigenetic remodeling occurs during the stage of immune response, signaling events imprint these stable programs are not well-defined. To gain insight into determinants effector-associated programming among cells, we explored role IL-12 in imprinting IFNg expression human priming. We observed TCR-mediated stimulation naïve sufficient demethylation promotor. However, TCR presence inflammatory cytokine, IL-12, resulted significant and locus was commensurate increase expression. further show IL-12-associated coupled division through TET2-dependent passive ex vivo CAR model system immunologically competent murine system. Collectively, data illustrate promotes TET2-mediated primary response serve as proof concept signal 3 cytokines can be used guide induction epigenetically regulated traits for adoptive immunotherapies.