{"doi":"10.1016/j.celrep.2021.109796","title":"Proinflammatory cytokines promote TET2-mediated DNA demethylation during CD8 T cell effector differentiation","abstract":"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.","journal":"Cell Reports","year":2021,"id":159303,"datarank":0.5641800173540344,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.0,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271004,"name":"Hossam A. Abdelsamed","orcid":"0000-0002-5448-6056","position":1,"is_corresponding":false},{"id":271008,"name":"Hazem E. Ghoneim","orcid":"0000-0002-9816-4286","position":2,"is_corresponding":false},{"id":271009,"name":"Shanta Alli","orcid":"0000-0003-1692-1616","position":3,"is_corresponding":false},{"id":636381,"name":"Charmaine Brown","orcid":"0000-0001-5716-9550","position":4,"is_corresponding":false},{"id":260229,"name":"Dalia Haydar","orcid":"0000-0002-7959-2699","position":5,"is_corresponding":false},{"id":302243,"name":"Mi Tian","orcid":"0000-0002-6446-1995","position":6,"is_corresponding":false},{"id":586264,"name":"Tarsha Harris","orcid":null,"position":7,"is_corresponding":false},{"id":271011,"name":"Maureen A. McGargill","orcid":"0000-0002-0916-0372","position":8,"is_corresponding":false},{"id":260238,"name":"Giedre Krenciute","orcid":"0000-0003-4335-0644","position":9,"is_corresponding":false},{"id":250684,"name":"Ben Youngblood","orcid":"0000-0002-1261-9957","position":10,"is_corresponding":false},{"id":271005,"name":"Caitlin C. Zebley","orcid":"0000-0002-8419-4660","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:44:35.165422Z","pmid":"34644568","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}