{"doi":"10.1126/sciimmunol.adu7341","title":"A linear ontogeny accounts for the development of naive, memory, and tumor-infiltrating regulatory T cells in mice","abstract":"Regulatory T cells (T reg cells) are critical regulators of adaptive immunity and the pathophysiology of antitumoral immunity. T reg cells are both generated during thymic development and induced from peripheral conventional T cells. How these distinct pathways contribute to the homeostasis of circulating T reg cells in health and disease remains unclear. We addressed this question using multiple fate-mapping mouse systems and modeling. Naive and effector/memory (EM) T reg cells exhibit distinct dynamics but are both continuously replenished by de novo generation throughout life. The predominant precursors of circulating EM T reg cells are naive thymic T reg cells and not conventional T cells, a process driven by self rather than foreign antigen recognition. Using the same fate reporters and three tumor models, we demonstrate that infiltrating T reg cells specifically derive from preexisting EM T reg cells. In summary, we define a linear ontogeny of T reg cells from the thymus to EM, driven by self-antigen recognition, that then gives rise to tumor-infiltrating T reg cells.","journal":"Science Immunology","year":2025,"id":531542,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":894034,"name":"Thea Hogan","orcid":"0000-0002-3140-0192","position":1,"is_corresponding":false},{"id":501247,"name":"Sanket Rane","orcid":"0000-0003-2612-4725","position":2,"is_corresponding":false},{"id":1350641,"name":"Yundi Huang","orcid":null,"position":3,"is_corresponding":false},{"id":501248,"name":"Claire Pearson","orcid":"0000-0001-5816-1657","position":4,"is_corresponding":false},{"id":1350381,"name":"Charles Sinclair","orcid":"0000-0001-6857-9993","position":5,"is_corresponding":false},{"id":250681,"name":"Simon T. Barry","orcid":"0000-0002-8511-0588","position":6,"is_corresponding":false},{"id":320578,"name":"Larissa S. Carnevalli","orcid":"0000-0001-7432-0195","position":7,"is_corresponding":false},{"id":431986,"name":"Andrew J. Yates","orcid":"0000-0003-4606-4483","position":8,"is_corresponding":false},{"id":501249,"name":"Benedict Seddon","orcid":"0000-0003-4352-3373","position":9,"is_corresponding":false},{"id":1350380,"name":"Sanmoy Pathak","orcid":"0000-0001-6137-8718","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:51:14.579161Z","pmid":"40540587","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":[]}