{"doi":"10.15252/embj.2020105220","title":"IL‐2/IL‐7‐inducible factors pioneer the path to T cell differentiation in advance of lineage‐defining factors","abstract":"When dormant naïve T cells first become activated by antigen-presenting cells, they express the autocrine growth factor IL-2 which transforms them into rapidly dividing effector T cells. During this process, hundreds of genes undergo epigenetic reprogramming for efficient activation, and also for potential reactivation after they return to quiescence as memory T cells. However, the relative contributions of IL-2 and T cell receptor signaling to this process are unknown. Here, we show that IL-2 signaling is required to maintain open chromatin at hundreds of gene regulatory elements, many of which control subsequent stimulus-dependent alternative pathways of T cell differentiation. We demonstrate that IL-2 activates binding of AP-1 and STAT5 at sites that can subsequently bind lineage-determining transcription factors, depending upon what other external factors exist in the local T cell environment. Once established, priming can also be maintained by the stroma-derived homeostatic cytokine IL-7, and priming diminishes if Il7r is subsequently deleted in vivo. Hence, IL-2 is not just a growth factor; it lays the foundation for T cell differentiation and immunological memory.","journal":"The EMBO Journal","year":2020,"id":96083,"datarank":1.163738330494004,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.6262104897255876,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.6262104897255876,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":31,"citers_with_citation_signal":28,"citers_with_endowment":28,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE147294"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":476808,"name":"Peter Keane","orcid":"0000-0001-8738-9693","position":1,"is_corresponding":false},{"id":476809,"name":"Jake K. Soley","orcid":"0000-0001-7131-2560","position":2,"is_corresponding":false},{"id":476810,"name":"Saskia Tauch","orcid":"0009-0001-3168-2038","position":3,"is_corresponding":false},{"id":338385,"name":"Dominika W. Gajdasik","orcid":null,"position":4,"is_corresponding":false},{"id":337027,"name":"Rémi Fiancette","orcid":"0000-0003-1531-9770","position":5,"is_corresponding":false},{"id":476811,"name":"Veronika Matei‐Rascu","orcid":"0000-0002-3786-4561","position":6,"is_corresponding":false},{"id":337029,"name":"Claire Willis","orcid":"0000-0001-5504-6741","position":7,"is_corresponding":false},{"id":337036,"name":"David R. Withers","orcid":"0000-0003-3757-7594","position":8,"is_corresponding":false},{"id":476812,"name":"Peter N. Cockerill","orcid":"0000-0002-4410-8174","position":9,"is_corresponding":false},{"id":337033,"name":"Sarah L. Bevington","orcid":"0000-0001-5108-7167","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-18T22:34:34.781847Z","pmid":"32930455","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":[]}