{"doi":"10.1126/sciadv.adi4310","title":"Lupus susceptibility gene <i>Pbx1</i> controls the development, stability, and function of regulatory T cells via <i>Rtkn2</i> expression","abstract":"The maintenance of regulatory T (T reg ) cells critically prevents autoimmunity. Pre–B cell leukemia transcription factor 1 ( Pbx1 ) variants are associated with lupus susceptibility, particularly through the expression of a dominant negative isoform Pbx1-d in CD4 + T cells. Pbx1-d overexpression impaired T reg cell homeostasis and promoted inflammatory CD4 + T cells. Here, we showed a high expression of Pbx1 in human and murine T reg cells, which is decreased in lupus patients and mice. Pbx1 deficiency or Pbx1-d overexpression reduced the number, stability, and suppressive activity of T reg cells, which increased murine responses to immunization and autoimmune induction. Mechanistically, Pbx1 deficiency altered the expression of genes implicated in cell cycle and apoptosis in T reg cells. Intriguingly, Rtkn2 , a Rho-GTPase previously associated with T reg homeostasis, was directly transactivated by Pbx1. Our results suggest that the maintenance of T reg cell homeostasis and stability by Pbx1 through cell cycle progression prevent the expansion of inflammatory T cells that otherwise exacerbates lupus progression in the hosts.","journal":"Science Advances","year":2024,"id":463851,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"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":863477,"name":"Yuk Pheel Park","orcid":"0000-0001-9749-5983","position":1,"is_corresponding":false},{"id":832008,"name":"Tracoyia Roach","orcid":"0000-0001-9431-6863","position":2,"is_corresponding":false},{"id":1294202,"name":"Damian Jimenez","orcid":"0009-0005-1234-8180","position":3,"is_corresponding":false},{"id":486441,"name":"Amanda Fisher","orcid":"0000-0002-2634-144X","position":4,"is_corresponding":false},{"id":946201,"name":"Mojgan Zadeh","orcid":"0000-0003-0407-0359","position":5,"is_corresponding":false},{"id":733982,"name":"Longhuan Ma","orcid":"0000-0002-1836-3462","position":6,"is_corresponding":false},{"id":608002,"name":"Eric S. Sobel","orcid":"0000-0003-3048-0589","position":7,"is_corresponding":false},{"id":617296,"name":"Yong Ge","orcid":null,"position":8,"is_corresponding":false},{"id":616023,"name":"Mansour Mohamadzadeh","orcid":"0000-0002-7356-7724","position":9,"is_corresponding":false},{"id":302973,"name":"Laurence Morel","orcid":"0000-0002-6622-1290","position":10,"is_corresponding":false},{"id":456371,"name":"Seung‐Chul Choi","orcid":"0000-0001-6230-9087","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:04:33.257852Z","pmid":"38536923","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":[]}