Tissue-resident, extravascular Ly6c-monocytes are critical for inflammation in the synovium

Monocytes are abundant immune cells that infiltrate inflamed organs. However, the majority of monocyte studies focus on circulating cells, rather than those in tissue. Here, we identify and characterize an intravas-cular synovial monocyte population resembling circulating non-classical monocytes and an extravascular tissue-resident monocyte-lineage cell (TR-MC) population distinct in surface marker and transcriptional pro-file from circulating monocytes, dendritic cells, and tissue macrophages that are conserved in rheumatoid arthritis (RA) patients. TR-MCs are independent of NR4A1 and CCR2, long lived, and embryonically derived. TR-MCs undergo increased proliferation and reverse diapedesis dependent on LFA1 in response to arthro-genic stimuli and are required for the development of RA-like disease. Moreover, pathways that are activated in TR-MCs at the peak of arthritis overlap with those that are downregulated in LFA1-/- TR-MCs. These find-ings show a facet of mononuclear cell biology that could be imperative to understanding tissue-resident myeloid cell function in RA.

Automated summary

This study identifies and characterizes distinct populations of monocytes in RA, including a synovial monocyte population resembling circulating non-classical monocytes and a tissue-resident monocyte-lineage cell population. These tissue-resident monocytes are long lived and embryonically derived, independent of NR4A1 and CCR2, and crucial for the development of RA-like disease. They undergo increased proliferation and reverse diapedesis in response to arthrogenic stimuli, and their activation pathways overlap with those downregulated in LFA1-/- TR-MCs.