{"doi":"10.1101/2025.01.08.631835","title":"T cells are necessary for development of PCOS reproductive symptoms in a letrozole-induced mouse model of PCOS","abstract":"Polycystic ovary syndrome (PCOS) is a complex condition with clear genetic susceptibilities that impact the heterogeneous clinical presentation of symptoms and severity through unknown mechanisms. Chronic inflammation is linked to PCOS, but a clear cause-and-effect relationship has yet to be established. This study used an in depth systems immunology approach and a letrozole-induced PCOS mouse model to identify changes in inflammatory factors associated with PCOS symptoms. By analyzing immune cells and secreted cytokines from 22 different mouse strains, we identified TNF-β as a key T cell-derived cytokine associated with PCOS, regardless of genetic background. We confirmed elevated TNF-β transcripts in immune cells from women with PCOS. Importantly, we used a knockout of TCRα to show that functional T cells are a necessary component of driving PCOS features in letrozole-treated female mice. These findings implicate T cells and specifically TNF-β production in the development of PCOS impairments. T cells are therefore an attractive target for the future development of anti-inflammatory therapeutics to improve PCOS symptoms.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557048,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"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":632561,"name":"Leandro M. Vélez","orcid":"0000-0001-8371-2633","position":1,"is_corresponding":false},{"id":499958,"name":"Gabriela De Robles","orcid":null,"position":2,"is_corresponding":false},{"id":1185687,"name":"Christy Nguyen","orcid":null,"position":3,"is_corresponding":false},{"id":1356740,"name":"Kiara Dominique Wiggins","orcid":null,"position":4,"is_corresponding":false},{"id":900810,"name":"Joshua K. Kim","orcid":"0000-0003-2606-6027","position":5,"is_corresponding":false},{"id":1456680,"name":"Naressa Naidu","orcid":"0009-0009-5610-4777","position":6,"is_corresponding":false},{"id":1452070,"name":"Julio A Ayala Angulo","orcid":null,"position":7,"is_corresponding":false},{"id":286313,"name":"Alexander S. Kauffman","orcid":"0000-0001-8631-6097","position":8,"is_corresponding":false},{"id":286312,"name":"Varykina G. Thackray","orcid":"0000-0002-6672-6117","position":9,"is_corresponding":false},{"id":1456681,"name":"Beata Banaszewska","orcid":"0000-0001-8492-7871","position":10,"is_corresponding":false},{"id":1456682,"name":"Ewa Wysocka","orcid":"0000-0002-4101-7656","position":11,"is_corresponding":false},{"id":584769,"name":"Antoni J. Dulęba","orcid":"0000-0003-1419-6502","position":12,"is_corresponding":false},{"id":236691,"name":"Marcus Seldin","orcid":"0000-0001-8026-4759","position":13,"is_corresponding":false},{"id":88595,"name":"Dequina Nicholas","orcid":"0000-0003-4996-2190","position":14,"is_corresponding":false},{"id":1357121,"name":"Naveena Ujagar","orcid":"0000-0003-1154-7063","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:55:13.130091Z","pmid":"39868135","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":[]}