{"doi":"10.1172/jci187862","title":"OCA-B promotes pathogenic maturation of stem-like CD4+ T cells and autoimmune demyelination","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 cells to promote autoimmune demyelination. Using 2 human multiple sclerosis (MS) datasets, we show that POU2AF1, the gene encoding OCA-B, is elevated in CD4+ T cells from patients with MS. 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 re-encounter, 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 time points, OCA-B loss results in both the accumulation of an immunomodulatory CD4+ T cell population expressing Ccr9 and Bach2, and loss of proinflammatory gene expression from Th17 cells. These results identify OCA-B as a driver of pathogenic CD4+ T cells.","journal":"Journal of Clinical Investigation","year":2025,"id":523205,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","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":79,"raw_metadata":null,"created_at":"2026-07-19T02:50:03.004175Z","pmid":"40299553","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":[]}