Resident synovial macrophages in synovial fluid: Implications for immunoregulation

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Resident synovial macrophages (RSMs) maintain joint immune homeostasis.
• Synovial barrier integrity is crucial for joint health.
• Breakdown of this barrier allows peripheral immune cell infiltration into synovial fluid (SF).

Purpose of the Study:

• To identify RSMs in human SF as a biomarker for synovial barrier integrity.
• To investigate the role of SF RSMs in inflammatory and septic arthritis.
• To explore the relationship between SF RSMs, synovial barrier damage, and joint pathology.

Main Methods:

• Analysis of human SF for RSM identification.
• Development of an ex vivo human synovium explant model.
• Single-cell RNA sequencing (scRNA-seq) of SF RSMs.
• Measurement of soluble RANKL (sRANKL) in SF.

Main Results:

• SF RSMs were identified and characterized.
• scRNA-seq revealed upregulation of pro-fibrotic and pro-osteoclastic pathways in SF RSMs from inflammatory arthritis patients.
• Increased RSM frequency in SF correlated with elevated sRANKL levels, irrespective of arthritis type.
• SF RSMs showed distinct pathway activation between inflammatory and septic arthritis.

Conclusions:

• RSM presence in SF can serve as an indirect indicator of synovial barrier damage.
• SF RSMs exhibit distinct molecular profiles in different arthritis types.
• Elevated sRANKL in SF may be linked to RSM presence and synovial barrier compromise.
• RSM frequency in SF may predict joint structure damage in arthritis.