{"doi":"10.1101/2024.03.04.583401","title":"Inducible deletion of <i>Ezh2</i> in CD4+ T cells inhibits kidney T cell infiltration and prevents interstitial nephritis in MRL/ <i>lpr</i> lupus-prone mice","abstract":"Systemic lupus erythematosus is a remitting relapsing autoimmune disease characterized by autoantibody production and multi-organ involvement. T cell epigenetic dysregulation plays an important role in the pathogenesis of lupus. We have previously demonstrated upregulation of the key epigenetic regulator EZH2 in CD4+ T cells isolated from lupus patients. To further investigate the role of EZH2 in the pathogenesis of lupus, we generated a tamoxifen-inducible CD4+ T cell Ezh2 conditional knockout mouse on the MRL/lpr lupus-prone background. We demonstrate that Ezh2 deletion abrogates lupus-like disease and prevents T cell differentiation. Single-cell analysis suggests impaired T cell function and activation of programed cell death pathways in EZH2-deficient mice. Ezh2 deletion in CD4+ T cells restricts TCR clonal repertoire and prevents kidney-infiltrating effector CD4+ T cell expansion and tubulointerstitial nephritis, which has been linked to end-stage renal disease in patients with lupus nephritis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":495082,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":265858,"name":"Mikhail G. Dozmorov","orcid":"0000-0002-0086-8358","position":1,"is_corresponding":false},{"id":1059600,"name":"Luis Espinoza","orcid":"0000-0002-4054-7487","position":2,"is_corresponding":false},{"id":1247833,"name":"Mckenna M Bowes","orcid":null,"position":3,"is_corresponding":false},{"id":284017,"name":"Sheldon Bastacky","orcid":"0000-0002-3173-5048","position":4,"is_corresponding":false},{"id":235896,"name":"Amr H. Sawalha","orcid":"0000-0002-3884-962X","position":5,"is_corresponding":false},{"id":702311,"name":"Xiaoqing Zheng","orcid":"0000-0002-0365-4953","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T02:09:15.528853Z","pmid":"38496595","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":[]}