{"doi":"10.1101/2023.11.29.569210","title":"OCA-B promotes pathogenic maturation of stem-like CD4 <sup>+</sup> T cells and autoimmune demyelination","abstract":"Abstract Stem-like T cells selectively contribute to autoimmunity, but the activities that promote their pathogenicity are incompletely understood. Here, we identify the transcription coregulator OCA-B as a driver of the pathogenic maturation of stem-like CD4 + T cell to promote autoimmune demyelination. Using two human multiple sclerosis (MS) datasets, we show that POU2AF1 , the gene encoding OCA-B, is elevated in CD4 + T cells from MS patients. We show that T cell-intrinsic OCA-B loss protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to viral CNS infection. In EAE models driven by antigen reencounter, OCA-B deletion nearly eliminates CNS infiltration, proinflammatory cytokine production and clinical disease. OCA-B-expressing CD4 + T cells of mice primed with autoantigen express an encephalitogenic gene program and preferentially confer disease. In a relapsing-remitting EAE model, OCA-B loss protects mice specifically at relapse. During remission, OCA-B promotes the expression of Tcf7 , Slamf6 , and Sell in proliferating CNS T cell populations. At relapse timepoints, OCA-B loss results in both the accumulation of an immunomodulatory CD4 + T cell population expressing Ccr9 and Bach2 , and loss of pro-inflammatory gene expression from Th17 cells. These results identify OCA-B as a driver of pathogenic CD4 + T cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":414529,"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":0.9562,"is_data_producer":false,"deposit_databanks":null,"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":306386,"name":"Amber R. Syage","orcid":null,"position":1,"is_corresponding":false},{"id":566369,"name":"Elnaz Mirzaei Mehrabad","orcid":"0000-0002-0393-0428","position":2,"is_corresponding":false},{"id":304483,"name":"Thomas E. Lane","orcid":"0000-0003-0392-0825","position":3,"is_corresponding":false},{"id":566372,"name":"Benjamin T. Spike","orcid":"0000-0002-0893-3302","position":4,"is_corresponding":false},{"id":15427,"name":"Dean Tantin","orcid":"0000-0003-1354-8385","position":5,"is_corresponding":false},{"id":577194,"name":"Erik P. Hughes","orcid":"0000-0001-8672-3928","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:22:05.177070Z","pmid":"38076925","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":[]}