Fig 1: Schematic Model of GM-CSF-CCL22 Axis in RA Pathogenesis. A STAT5 Activation in RA Monocytes: Peripheral blood monocytes from RA patients exhibit enhanced STAT5 phosphorylation (p-STAT5), priming them for hyperactivation and differentiation into pro-inflammatory M1 macrophages; B GM-CSF Drives M1 Polarization: In the synovial microenvironment, GM-CSF (↑ in RA synovium) promotes monocyte differentiation into M1 macrophages; C Metabolic Reprogramming: RA GM-DMs display a hypermetabolic phenotype with enhanced oxidative phosphorylation but impaired glycolysis, favoring sustained inflammatory activity; D CCL22-Mediated T Cell Recruitment and Polarization: GM-DMs secrete CCL22, which: (a) recruits CD4 + T cells2; (b) promotes Th1/Th17 differentiation; E Inflammatory Cascade and Joint Destruction: Th1/Th17-derived cytokines synergize with macrophage-produced mediators to drive synovitis, cartilage erosion, and bone damage