{"doi":"10.1084/jem.20200533","title":"Targeting transcriptional coregulator OCA-B/Pou2af1 blocks activated autoreactive T cells in the pancreas and type 1 diabetes","abstract":"The transcriptional coregulator OCA-B promotes expression of T cell target genes in cases of repeated antigen exposure, a necessary feature of autoimmunity. We hypothesized that T cell-specific OCA-B deletion and pharmacologic OCA-B inhibition would protect mice from autoimmune diabetes. We developed an Ocab conditional allele and backcrossed it onto a diabetes-prone NOD/ShiLtJ strain background. T cell-specific OCA-B loss protected mice from spontaneous disease. Protection was associated with large reductions in islet CD8+ T cell receptor specificities associated with diabetes pathogenesis. CD4+ clones associated with diabetes were present but associated with anergic phenotypes. The protective effect of OCA-B loss was recapitulated using autoantigen-specific NY8.3 mice but diminished in monoclonal models specific to artificial or neoantigens. Rationally designed membrane-penetrating OCA-B peptide inhibitors normalized glucose levels and reduced T cell infiltration and proinflammatory cytokine expression in newly diabetic NOD mice. Together, the results indicate that OCA-B is a potent autoimmune regulator and a promising target for pharmacologic inhibition.","journal":"The Journal of Experimental Medicine","year":2020,"id":97483,"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":33,"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":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":482413,"name":"Jelena Perovanović","orcid":"0000-0003-2348-2332","position":1,"is_corresponding":false},{"id":15423,"name":"Arvind Shakya","orcid":"0000-0001-7993-6159","position":2,"is_corresponding":false},{"id":80262,"name":"Zuolian Shen","orcid":null,"position":3,"is_corresponding":false},{"id":482414,"name":"Cody N. German","orcid":"0000-0002-8035-7274","position":4,"is_corresponding":false},{"id":482415,"name":"Andrea Ibarra","orcid":"0000-0002-7346-2068","position":5,"is_corresponding":false},{"id":483685,"name":"Jillian L. Jafek","orcid":null,"position":6,"is_corresponding":false},{"id":483686,"name":"Nai-Pin Lin","orcid":null,"position":7,"is_corresponding":false},{"id":388823,"name":"Brian D. Evavold","orcid":"0000-0002-3561-3494","position":8,"is_corresponding":false},{"id":482416,"name":"Danny Hung‐Chieh Chou","orcid":"0000-0001-9110-614X","position":9,"is_corresponding":false},{"id":379438,"name":"Peter E. Jensen","orcid":"0000-0002-1639-8223","position":10,"is_corresponding":false},{"id":379437,"name":"Xiao He","orcid":"0000-0002-9286-9859","position":11,"is_corresponding":false},{"id":15427,"name":"Dean Tantin","orcid":"0000-0003-1354-8385","position":12,"is_corresponding":false},{"id":482412,"name":"Heejoo Kim","orcid":"0000-0003-0358-2416","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T22:36:02.818637Z","pmid":"33295943","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":[]}