{"doi":"10.1073/pnas.2002266117","title":"Impaired estrogen signaling underlies regulatory T cell loss-of-function in the chronically inflamed intestine","abstract":"Significance This study identifies a mechanism by which 17β estradiol (estrogen) contributes to peripheral tolerance via modulation of regulatory T cell (Treg) differentiation and function. Our results show that estrogen signaling through the nuclear receptor ERβ is required for TGF-β–dependent differentiation of Tregs, a critical pathway for peripheral Treg differentiation in the gut. Female patients with Crohn’s disease express significantly lower levels of ERβ in peripheral T cells and the intestinal mucosae. Tregs deficient in ERβ express aberrant levels of Tsc22d3 (GILZ), a protein not normally expressed in Tregs and that interferes with functional Treg suppression. Our findings support a pathway by which ERβ-specific signaling normally functions to limit GILZ expression in Tregs, thus maintaining peripheral tolerance in the gut.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":56334,"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":86,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"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":293772,"name":"Sarah Bedoyan","orcid":null,"position":1,"is_corresponding":false},{"id":293773,"name":"Hannah Havran","orcid":null,"position":2,"is_corresponding":false},{"id":292534,"name":"Brian Richardson","orcid":"0000-0002-7332-9152","position":3,"is_corresponding":false},{"id":105516,"name":"Mark J. Cameron","orcid":"0000-0003-4768-4094","position":4,"is_corresponding":false},{"id":240325,"name":"Theresa T. Pizarro","orcid":"0000-0003-3163-915X","position":5,"is_corresponding":false},{"id":292533,"name":"Wendy A. Goodman","orcid":"0000-0002-6864-0384","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T21:05:49.581291Z","pmid":"32632016","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":[]}