20.500.12556/DiRROS-29643 HLA-DR–expressing fibroblast-like synoviocytes are inducible antigen presenting cells that present autoantigens in Lyme arthritis 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. Lyme arthritis autoimmune diseases infectious disease true false true Angleški jezik Ni določen Neznano 2026-06-02 09:46:45 2026-06-02 09:46:45 2026-06-03 03:56:36 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 25. 5. 2026; str. 678-689 issue 10 Vol. 6 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.9 2578-5745 10.1002/acr2.11710 279250691 RAZ_Rouse_Joseph_R._2024.pdf RAZ_Rouse_Joseph_R._2024.pdf 1 EEE48FBBB463530321950D5E44A26A90 e853897a4238a5d480a59449bf478d9e0f527badfeee98801e00b89450d0e437 6008ebbb-5e57-11f1-8e51-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44514 https://acrjournals.onlinelibrary.wiley.com/doi/full/10.1002/acr2.11710 1 353f9624-5e57-11f1-8e51-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44513 Univerzitetni klinični center Ljubljana 0 0 0