{"doi":"10.1002/acr2.11710","title":"<scp>HLA</scp>‐<scp>DR</scp>–Expressing Fibroblast‐Like Synoviocytes Are Inducible Antigen Presenting Cells That Present Autoantigens in Lyme Arthritis","abstract":"OBJECTIVE: HLA-DR-expressing fibroblast-like synoviocytes (FLS) are a prominent cell type in synovial tissue in chronic inflammatory forms of arthritis. FLS-derived extracellular matrix (ECM) proteins, including fibronectin-1 (FN1), contain immunogenic CD4+ T cell epitopes in patients with postinfectious Lyme arthritis (LA). However, the role of FLS in presentation of these T cell epitopes remains uncertain. METHODS: Primary LA FLS and primary murine FLS stimulated with interferon gamma (IFNγ), Borrelia burgdorferi, and/or B burgdorferi peptidoglycan (PG) were assessed for properties associated with antigen presentation. HLA-DR-presented peptides from stimulated LA FLS were identified by immunopeptidomics analysis. OT-II T cells were co-cultured with stimulated murine FLS in the presence of cognate ovalbumin antigen to determine the potential of FLS to act as inducible antigen presenting cells (APCs). RESULTS: FLS expressed HLA-DR molecules within inflamed synovial tissue and tendons from patients with postinfectious LA in situ. Major histocompatibility complex (MHC) class II and co-stimulatory molecules were expressed by FLS following in vitro stimulation with IFNγ and B burgdorferi and presented both foreign and self-MHC-II peptides, including an immunogenic T cell epitope derived from Lyme autoantigen FN1. Stimulated FLS induced proliferation of naive OT-II CD4+ T cells that were dependent on OT-II antigen and CD40. Stimulation with B burgdorferi PG enhanced FLS-mediated T cell activation. CONCLUSION: MHC-II+ FLS are inducible APCs that can induce CD4+ T cell activation in an antigen- and CD40-dependent manner. Activated FLS can also present ECM-derived Lyme autoantigens, implicating FLS in amplifying tissue-localized autoimmunity in LA.","journal":"ACR Open Rheumatology","year":2024,"id":432394,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1173577,"name":"Rebecca Danner","orcid":"0000-0003-2238-0916","position":1,"is_corresponding":false},{"id":1173966,"name":"Amanda Wahhab","orcid":null,"position":2,"is_corresponding":false},{"id":434293,"name":"Michaela Pereckas","orcid":"0000-0002-7287-5450","position":3,"is_corresponding":false},{"id":810161,"name":"Christine Nguyen","orcid":"0000-0002-5750-8134","position":4,"is_corresponding":false},{"id":627755,"name":"Mecaila E. McClune","orcid":"0000-0002-9071-540X","position":5,"is_corresponding":false},{"id":311008,"name":"Allen C. Steere","orcid":"0000-0002-5268-9853","position":6,"is_corresponding":false},{"id":482773,"name":"Klemen Strle","orcid":"0000-0002-0109-6791","position":7,"is_corresponding":false},{"id":627751,"name":"Brandon L. Jutras","orcid":"0000-0002-7989-1031","position":8,"is_corresponding":false},{"id":744999,"name":"Robert B. Lochhead","orcid":"0000-0001-7726-0466","position":9,"is_corresponding":false},{"id":1173576,"name":"Joseph R Rouse","orcid":"0000-0001-8675-904X","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:59:35.267142Z","pmid":"39073021","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":[]}