Work

204 Selective Deletion of Cells Expressing Fibroblast Activation Protein Attenuates Synovial Inflammation

Year: 2016

Type: article

Abstract: Background: Synovial fibroblasts are key effector cells of synovial inflammation and joint damage in RA. Fibroblast activation protein (FAP) is a cell surface serine protease expressed by synovial fibroblasts and upregulated during synovial inflammation. It has previously been demonstrated that in the absence of FAP, mice have less cartilage degradation following the induction of inflammatory arthritis. Despite these observations, little is unknown about the pathogenic role of FAP-expressing fibroblasts in inflammatory arthritis. Methods: To determine the role of FAP-expressing fibroblasts we utilized a transgenic mouse in which FAP-expressing cells can be ablated. Inflammatory polyarthritis was induced in mice using a transient erosive antibody-induced (K/BxN serum transfer) inflammatory arthritis model. Mice were scored for clinical signs of inflammatory arthritis and flow cytometry of digested synovial tissue was performed to determine the relative expression of fibroblast subsets. Results: FAP was dynamically expressed by synovial fibroblasts, with upregulated expression observed during active synovial inflammation. FAP was predominately expressed by lining layer synovial fibroblasts, and a subpopulation of FAP-expressing cells also expressed podoplanin. Selective deletion of FAP-expressing cells before the transfer of arthrogenic K/BxN serum resulted in the delayed onset of inflammatory arthritis, but with similar severity to control mice. In contrast, therapeutic deletion of FAP-expressing cells in established inflammatory arthritis significantly attenuated the clinical signs of synovial inflammation.

Source: Lara D. Veeken

DOI: 10.1093/rheumatology/kew173.001