{"doi":"10.7554/elife.76927.sa0","title":"Editor's evaluation: 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":null,"year":2022,"id":314427,"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":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":446893,"name":"Apurva Sarin","orcid":"0000-0003-0851-4818","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:33:52.047924Z","pmid":null,"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":[]}