摘要Background:To study the relationships among emodin,synovial fibroblasts(FLSs),and macrophages(STMs)to provide guidance for the use of emodin in rheumatoid arthritis(RA)treatment.Methods:RA clinical samples from patients with different pathological processes were collected,and the correlations between the subsets of FLSs and STMs and path-ological processes were analyzed via flow cytometry.In vitro experimental methods such as enzyme linked immunosorbent assay(ELISA),Western blotting,Transwell as-says,CCK-8 assays and cell coculture were used to assess cell proliferation,migration and secretion of inflammatory factors.A collagen-induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytom-etry,micro-CT and staining.Results:Unique subsets of FLSs and STMs,namely,FAPα+THY1-FLSs,FAPα+THY1+FLSs,and MerTKposTREM2high STMs,were identified in synovial tissues from RA patients.The number of MerTKposTREM2high STMs was negatively correlated with the degree of damage in RA,while the number of FAPα+THY1-FLSs was positively correlated with damage.On the one hand,emodin promoted the aggregation of MerTKposTREM2high STMs.Moreover,MerTKposTREM2high STM-mediated secre-tion of exosomes was promoted,which can inhibit the secretion of pro-inflammatory factors by FAPα+THY1+FLSs and promote the secretion of anti-inflammatory factors by FAPα+THY1+FLSs,thereby inhibiting FAPα+THY1-FLS proliferation and migration,improving the local immune microenvironment,and inhibiting RA damage.Conclusion:Emodin was shown to regulate the aggregation of STM subsets and exo-some secretion,affecting the secretion,proliferation and migration of inflammatory factors in FLS subsets,and ultimately achieving good therapeutic efficacy in RA pa-tients,suggesting that it has important clinical value.