Perivascular RELMα-positive synovial macrophages recruit monocytes at the onset of inflammatory arthritis

Area of Science:

• Immunology
• Cell Biology
• Rheumatology

Background:

• Myeloid cells like macrophages, monocytes, and neutrophils are key in inflammatory diseases such as rheumatoid arthritis (RA).
• Synovial macrophages exhibit diversity, but their locations and functions, apart from lining macrophages, are poorly understood.

Purpose of the Study:

• To investigate the specific roles and locations of diverse synovial macrophage populations in early inflammatory arthritis.
• To elucidate the mechanisms by which macrophages contribute to monocyte recruitment and differentiation in the synovium.

Main Methods:

• Utilized scRNA-seq data to identify macrophage populations.
• Employed reporter mouse models (CCL2mCherry and CCR2CRE/mKate2) to track specific cell types and chemokine production.
• Localized RELMα-positive macrophages to the synovial interstitium near blood vessels.

Main Results:

• RELMα-positive macrophages were identified in the synovial interstitium, adjacent to blood vessels.
• These macrophages secrete CCL2, a chemokine that recruits monocytes.
• Monocyte recruitment is predominantly directed to the synovial interstitium during antigen-induced arthritis.
• Recruited monocytes differentiate into tissue-resident macrophages, including VSIG4-expressing cells similar to lining macrophages.

Conclusions:

• RELMα-positive macrophages play a critical role in orchestrating monocyte recruitment to the synovium during articular inflammation.
• This recruitment contributes to the replenishment of synovial lining macrophages, impacting the inflammatory response in RA.