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

Abstract

Synovial fluid (SF)-derived monocyte-macrophage (MON-Mf)-lineage cells in knee osteoarthritis (KOA) remain poorly understood. We analyzed SF samples from 420 patients with KOA with effusion. The MONMf 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-Mf subpopulations and highlighted the role of inactive mDCs in KOA.