{"doi":"10.1002/eji.202350548","title":"MicroRNAs targeting TGF‐β signaling exacerbate central nervous system autoimmunity by disrupting regulatory T cell development and function","abstract":"Transforming growth factor beta (TGF-β) signaling is essential for a balanced immune response by mediating the development and function of regulatory T cells (Tregs) and suppressing autoreactive T cells. Disruption of this balance can result in autoimmune diseases, including multiple sclerosis (MS). MicroRNAs (miRNAs) targeting TGF-β signaling have been shown to be upregulated in naïve CD4 T cells in MS patients, resulting in a limited in vitro generation of human Tregs. Utilizing the murine model experimental autoimmune encephalomyelitis, we show that perinatal administration of miRNAs, which target the TGF-β signaling pathway, enhanced susceptibility to central nervous system (CNS) autoimmunity. Neonatal mice administered with these miRNAs further exhibited reduced Treg frequencies with a loss in T cell receptor repertoire diversity following the induction of experimental autoimmune encephalomyelitis in adulthood. Exacerbated CNS autoimmunity as a result of miRNA overexpression in CD4 T cells was accompanied by enhanced Th1 and Th17 cell frequencies. These findings demonstrate that increased levels of TGF-β-associated miRNAs impede the development of a diverse Treg population, leading to enhanced effector cell activity, and contributing to an increased susceptibility to CNS autoimmunity. Thus, TGF-β-targeting miRNAs could be a risk factor for MS, and recovering optimal TGF-β signaling may restore immune homeostasis in MS patients.","journal":"European Journal of Immunology","year":2024,"id":479946,"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":0.9459,"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":1319629,"name":"Mary Severin","orcid":null,"position":1,"is_corresponding":false},{"id":460192,"name":"Priscilla W. Lee","orcid":null,"position":2,"is_corresponding":false},{"id":1282389,"name":"Joshua L. Deffenbaugh","orcid":"0000-0002-5353-5709","position":3,"is_corresponding":false},{"id":1129991,"name":"Yue Liu","orcid":"0000-0002-7623-4431","position":4,"is_corresponding":false},{"id":1086841,"name":"Shawn P. Murphy","orcid":"0009-0004-9216-3153","position":5,"is_corresponding":false},{"id":1282775,"name":"Cora L. Petersen‐Cherubini","orcid":null,"position":6,"is_corresponding":false},{"id":458909,"name":"Amy E. Lovett‐Racke","orcid":"0000-0003-1379-1625","position":7,"is_corresponding":false},{"id":385085,"name":"Christina N. Rau","orcid":"0000-0001-8825-1821","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T02:06:58.305365Z","pmid":"38634287","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":[]}