Background/Purpose: Macrophages in the synovial lining of the joint are critical players in the pathogenesis of rheumatoid arthritis (RA). However, their heterogeneity remains poorly characterized.

Methods: Using single cell RNA-sequencing (scRNA-seq), we uncovered 4 distinct subsets of mouse synovial macrophages during steady state distinguishable by expressions of CX3CR1 and MHCII.

Results: MHCII- subsets preferentially expressed markers associated with tissue-residency, including Sepp1 and C1qc, whereas MHCII+ subsets expressed monocyte-associated markers such as Ccr2 and Cd74, Ly6c2, a key maker of classical monocytes, was expressed only in CX3CR1+MHCII+ subset. Fate mapping experiments confirmed the differing ontogenies of synovial macrophage subsets. During inflammatory conditions (serum transfer induced arthritis), we observed the expansion of CX3CR1+MHCII+ subset and increased expression of monocyte-associated genes in all macrophages, which coincides with the recruitment of circulating monocytes. These subsets are recapitulated in scRNA-seq data from synovial biopsies of RA patients.

Conclusion: Our results support a dynamic role for synovial macrophages in inflammation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-cell-rna-sequencing-reveals-distinct-macrophage-subsets-in-the-joint-with-differing-ontogenies-during-steady-state-and-arthritis/