{"doi":"10.7554/elife.76927","title":"The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate","abstract":"Genes associated with increased susceptibility to multiple sclerosis (MS) have been identified, but their functions are incompletely understood. One of these genes codes for the RNA helicase DExD/H-Box Polypeptide 39B (DDX39B), which shows genetic and functional epistasis with interleukin-7 receptor-α gene ( IL7R ) in MS-risk. Based on evolutionary and functional arguments, we postulated that DDX39B enhances immune tolerance thereby decreasing MS risk. Consistent with such a role we show that DDX39B controls the expression of many MS susceptibility genes and important immune-related genes. Among these we identified Forkhead Box P3 ( FOXP3 ), which codes for the master transcriptional factor in CD4 + /CD25 + T regulatory cells. DDX39B knockdown led to loss of immune-regulatory and gain of immune-effector expression signatures. Splicing of FOXP3 introns, which belong to a previously unrecognized type of introns with C-rich polypyrimidine tracts, was exquisitely sensitive to DDX39B levels. Given the importance of FOXP3 in autoimmunity, this work cements DDX39B as an important guardian of immune tolerance.","journal":"eLife","year":2023,"id":332032,"datarank":0.744636911898924,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.2502613819982745,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.2502613819982745,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":20,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE145773"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":748536,"name":"Gaddiel Galarza-Muñoz","orcid":"0009-0008-2814-8783","position":1,"is_corresponding":false},{"id":698963,"name":"Chloe K. Nagasawa","orcid":"0000-0002-4550-1381","position":2,"is_corresponding":false},{"id":749109,"name":"Geraldine Schott","orcid":null,"position":3,"is_corresponding":false},{"id":411014,"name":"Liuyang Wang","orcid":"0000-0001-9556-2361","position":4,"is_corresponding":false},{"id":411013,"name":"Alejandro L. Antonia","orcid":"0000-0003-4387-6398","position":5,"is_corresponding":false},{"id":229144,"name":"Vaibhav Jain","orcid":"0000-0003-2394-3426","position":6,"is_corresponding":false},{"id":371896,"name":"Xiaoying Yu","orcid":"0000-0003-1659-2365","position":7,"is_corresponding":false},{"id":225076,"name":"Steven G. Widen","orcid":"0000-0002-6512-363X","position":8,"is_corresponding":false},{"id":340297,"name":"Farren Briggs","orcid":"0000-0003-0903-1359","position":9,"is_corresponding":false},{"id":59323,"name":"Simon G. Gregory","orcid":"0000-0002-7805-1743","position":10,"is_corresponding":false},{"id":411019,"name":"Dennis C. Ko","orcid":"0000-0002-0113-5981","position":11,"is_corresponding":false},{"id":494382,"name":"W. Samuel Fagg","orcid":"0000-0003-2909-1666","position":12,"is_corresponding":false},{"id":276957,"name":"Shelton S. Bradrick","orcid":"0000-0003-1566-9797","position":13,"is_corresponding":false},{"id":232721,"name":"Mariano A. García-Blanco","orcid":"0000-0001-8538-1997","position":14,"is_corresponding":false},{"id":495013,"name":"Minato Hirano","orcid":null,"position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T01:09:25.015646Z","pmid":"37261960","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":[]}