biostudies-literatureUnknownRouse JRNIAID NIH HHS<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.bioRxiv : the preprint server for biology2023.11.21.568066https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690166biostudies-literatureHuman leukocyte antigen HLA-DR-expressing fibroblast-like synoviocytes are inducible antigen presenting cells that present autoantigens in Lyme arthritis.PMC10690166R21 AI148982R01 AI178711R01 AI173256Rouse JRPereckas MSteere ACDanner RStrle KJutras BLMcClune MELochhead RBWahhab AfalseHuman leukocyte antigen HLA-DR-expressing fibroblast-like synoviocytes are inducible antigen presenting cells that present autoantigens in Lyme arthritis.<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.2023-01-01T00:00:00Z2023 Nov2025-04-22T11:24:10.906Z2025-04-05T23:52:07.848ZS-EPMC106901663804540710.1101/2023.11.21.568066