Complexity of synovial fluid-derived monocyte-macrophage-lineage cells in knee osteoarthritis

Synovial fluid (SF)-derived monocyte-macrophage (MON-Mϕ)-lineage cells in knee osteoarthritis (KOA) remain poorly understood. We analyzed SF samples from 420 patients with KOA with effusion. The MON-Mϕ cells accounted for 47.4% (median; range 7.1%-94.4%) of CD45⁺ cells and consisted of four subpopulations that correlated with the distribution and activation of other immune cells. The most abundant subpopulation was that of inactive CD11b⁺CD14^-CD16^- myeloid dendritic cells (mDCs; cDC2), which exhibited low cytokine production, low T lymphocyte stimulation, and high migratory ability. Other major subpopulations included CD11b⁺CD14⁺CD16^- monocyte-like cells and CD11b⁺CD14⁺CD16⁺ macrophages, which share a similar transcriptomic profile. A subpopulation of CD11b^-CD14^-CD16^- mDCs (cDC1) was less common. A higher proportion of CD11b⁺CD14^-CD16^- mDCs was linked to early-stage KOA and mild joint pain. Dendritic cells were rarely present in KOA synovium. This study revealed the considerable complexity of SF-derived MON-Mϕ subpopulations and highlighted the role of inactive mDCs in KOA.