Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the...

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Synovial tissue-resident macrophages (STRMs) are crucial for maintaining joint homeostasis.
• In rheumatoid arthritis (RA), infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) are known to play pro-inflammatory roles.
• The specific roles and functional changes of STRMs in the RA joint environment remain unclear.

Purpose of the Study:

• To investigate the phenotypic and functional alterations of STRMs in response to rheumatoid arthritis (RA)-associated stimuli in vitro.
• To compare the responses of STRMs with those of peripheral blood monocyte-derived macrophages (PBMoMs) under RA-related conditions.

Main Methods:

• STRMs were isolated from osteoarthritis (OA) synovium, and PBMoMs were prepared for comparison.
• Cells were stimulated with plate-bound IgG (mimicking RA immune complexes) or combinations of inflammatory mediators (TNF-α, PGE2, IFN-γ).
• Changes in surface marker and cytokine gene expression were analyzed, along with the impact on cocultured synovial fibroblasts.

Main Results:

• PBMoMs exhibited a clear shift towards a pro-inflammatory phenotype upon stimulation.
• STRMs showed minimal changes in surface molecule and marker gene expression but altered cytokine gene expression patterns, similar to PBMoMs.
• In vitro stimulated STRMs promoted pro-inflammatory functions in cocultured synovial fibroblasts.

Conclusions:

• STRMs may contribute to pro-inflammatory processes in RA joints.
• Despite RA-related stimuli, STRMs appear to largely maintain their characteristic steady-state phenotypes.
• STRMs' altered cytokine profiles and effects on synovial fibroblasts suggest a potential pro-inflammatory role in RA pathogenesis.