Synovial macrophages are critical to tissue maintenance and immune homeostasis in the joints. However, the function of synovial macrophages is compromised with age leading to increased susceptibility to chronic inflammation and arthritis. Here, we compare synovial macrophage composition and transcriptional profiles in young vs. old joints from male and female mice using single-cell RNA sequencing with cell-surface protein detection (CITE-seq).
We defined five major synovial macrophage subpopulations: CX3CR1+ lining, CD163+ interstitial, MHCII+ monocyte-derived, Ly6C+ infiltrating, and Ctsk-expressing osteoclast-like cells, across age and sex. Ly6C+ macrophages were expanded in old mice of both sexes compared to young, while CX3CR1+ lining macrophages were reduced. MHCII+ macrophage proportion differed between sexes, with Arg1-expressing cells driving an increase in females and a decrease in males with age.