{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Rouse JR"],"funding":["NIAID NIH HHS"],"pubmed_abstract":["<h4>Background</h4>HLA-DR-expressing fibroblast-like synoviocytes (FLS) are a prominent cell type in synovial tissue in chronic inflammatory forms of arthritis. We recently showed that peptides from several extracellular matrix (ECM) proteins, including fibronectin-1 (FN1), contained 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.<h4>Methods</h4>Primary LA FLS and primary murine FLS stimulated with interferon gamma (IFNγ), <i>Borrelia burgdorferi</i>, and/or <i>B. burgdorferi</i> 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 cocultured with stimulated murine FLS in the presence of cognate ovalbumin antigen to determine the potential of FLS to act as inducible antigen presenting cells (APC).<h4>Results</h4>FLS expressed HLA-DR molecules within inflamed synovial tissue and tendons from patients with post-infectious LA patients <i>in situ.</i> MHC class II and costimulatory molecules were expressed by FLS following <i>in vitro</i> stimulation with IFNγ and <i>B. burgdorferi</i> and presented both foreign and self MHC-II peptides, including T cell epitopes derived from two Lyme autoantigens fibronectin-1 (FN1) and endothelial cell growth factor (ECGF). Stimulated murine FLS induced proliferation of naïve OT-II CD4+ T cells, particularly when FLS were stimulated with both IFNγ and PG.<h4>Conclusions</h4>MHC-II+ FLS are inducible APCs that can induce CD4+ T cell activation and can present Lyme autoantigens derived from ECM proteins, thereby amplifying tissue-localized autoimmune CD4+ T cell responses in LA."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.11.21.568066"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690166"],"repository":["biostudies-literature"],"pubmed_title":["Human leukocyte antigen HLA-DR-expressing fibroblast-like synoviocytes are inducible antigen presenting cells that present autoantigens in Lyme arthritis."],"pmcid":["PMC10690166"],"funding_grant_id":["R21 AI148982","R01 AI178711","R01 AI173256"],"pubmed_authors":["Rouse JR","Pereckas M","Steere AC","Danner R","Strle K","Jutras BL","McClune ME","Lochhead RB","Wahhab A"],"additional_accession":[]},"is_claimable":false,"name":"Human leukocyte antigen HLA-DR-expressing fibroblast-like synoviocytes are inducible antigen presenting cells that present autoantigens in Lyme arthritis.","description":"<h4>Background</h4>HLA-DR-expressing fibroblast-like synoviocytes (FLS) are a prominent cell type in synovial tissue in chronic inflammatory forms of arthritis. We recently showed that peptides from several extracellular matrix (ECM) proteins, including fibronectin-1 (FN1), contained 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.<h4>Methods</h4>Primary LA FLS and primary murine FLS stimulated with interferon gamma (IFNγ), <i>Borrelia burgdorferi</i>, and/or <i>B. burgdorferi</i> 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 cocultured with stimulated murine FLS in the presence of cognate ovalbumin antigen to determine the potential of FLS to act as inducible antigen presenting cells (APC).<h4>Results</h4>FLS expressed HLA-DR molecules within inflamed synovial tissue and tendons from patients with post-infectious LA patients <i>in situ.</i> MHC class II and costimulatory molecules were expressed by FLS following <i>in vitro</i> stimulation with IFNγ and <i>B. burgdorferi</i> and presented both foreign and self MHC-II peptides, including T cell epitopes derived from two Lyme autoantigens fibronectin-1 (FN1) and endothelial cell growth factor (ECGF). Stimulated murine FLS induced proliferation of naïve OT-II CD4+ T cells, particularly when FLS were stimulated with both IFNγ and PG.<h4>Conclusions</h4>MHC-II+ FLS are inducible APCs that can induce CD4+ T cell activation and can present Lyme autoantigens derived from ECM proteins, thereby amplifying tissue-localized autoimmune CD4+ T cell responses in LA.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2025-04-22T11:24:10.906Z","creation":"2025-04-05T23:52:07.848Z"},"accession":"S-EPMC10690166","cross_references":{"pubmed":["38045407"],"doi":["10.1101/2023.11.21.568066"]}}