Complexity of synovial fluid-derived monocyte-macrophage-lineage cells in knee osteoarthritis
Zuzana Mikulková, Jiří Gallo, Gayane Manukyan, Markéta Trajerová, Jakub Savara, Bishu Shrestha, Tereza Dýšková, Romana Nesnadna, Zuzana Slobodová, Michal Štefančík, Eva Kriegová
Abstract
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.