Expanded CD1c+CD163+ DC3s population in synovial tissues is associated with disease progression of osteoarthritis

Objective: The mechanisms underlying osteoarthritis (OA) have recently been hypothesized to involve a dysfunctional immune system. This study aimed to evaluate the landscape of immune cells infiltrating synovial tissue and to determine their function in OA progression.Design: Synovial tissue, synovium fluid (SF) and peripheral blood were collected from 21 patients with OA. Mononuclear cells were isolated and characterized using flow cytometry. H&E staining and multiplex immunohistochemistry (mIHC) histological assessment of synovial samples were performed. Cytokine levels in the SF were measured using ELISA.Results: We observed similar frequencies of immune cells in the synovium and SF, which were enriched in macrophages, T cells, and DCs. Notably, DC3s, CD1c+DC163+ 36 DCs, an inflammation-induced subpopulation of DCs, was significantly expanded in 37 the synovium and SF. Furthermore, we found that DC3s were primarily located within 38 the ectopic lymphoid-like structure (ELLS) in close proximity to CD8+ T cells. Finally, 39 the level of TNF-α and IL12p70 in the SF correlated with the severity of OA, suggesting 40 a possible link between DC3s and OA progression.Conclusion: These data suggest that OA is an immune system-related disease and that DC3s may play an active role in OA progression by promoting ELLS formation and inflammatory responses.