Perivascular RELM-positive synovial macrophages recruit monocytes at the onset of inflammatory arthritis
Schonfeldova, B.; Chibwana, M.; Gentek, R.; Zec, K.; Udalova, I. A.
Show abstract
Macrophages, monocytes and neutrophils are major types of myeloid cells involved in inflammatory diseases, such as rheumatoid arthritis (RA). Recent scRNA-seq studies identified a remarkable diversity of synovial macrophages but, with the exception of lining macrophages, their geographical location and specific roles remain largely unexplored. Here, we localised the RELM-positive macrophages, predicted to produce high levels of monocyte-recruiting chemokines, to the synovial interstitium and more specifically, to the vicinity of interstitial blood vessels. Using complementary reporter mouse models, CCL2mCherry to label CCL2-producing cells, and CCR2CRE/mKate2 marking CCR2 expressing monocytes, we demonstrated that RELM-positive perivascular macrophages secrete CCL2 to recruit monocytes predominantly to the synovial interstitium at the onset of antigen-induced arthritis. The inflamed synovial environment guides the differentiation of the recruited monocytes into tissue-resident macrophages, including but not limited to macrophages expressing VSIG4, a characteristic marker of lining macrophages. Thus, RELM-positive macrophages orchestrate monocyte recruitment to the synovium during articular inflammation, contributing to a local replenishment of synovial lining macrophages.
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