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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and progressive joint destruction, driven by complex pathogenic mechanisms. Aberrant activation of various cellular components and their dynamic interactions contribute significantly to the onset and progression of RA. Key cell types involved include non-immune cells, such as fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS), innate immune cells (neutrophils, dendritic cells, and macrophages) and adaptive immune cells (B cells and T cells). These cells collectively release high levels of proinflammatory cytokines (e.g., TNF, IL-1β, IL-6, IL-17, GM-CSF, and lymphotoxins), chemokines (e.g., CCL17, CCL22, CXCL8 and CXCL10), growth factors (e.g., PDGF, and TGF-β), pro-angiogenic factors (e.g., VEGF and FGF), matrix metalloproteinases (e.g., MMP2 and MMP9), and autoantibodies (e.g., RF and ACPA) that collectively contribute to maintaining an inflammatory microenvironment in RA joints. These molecular mediators recruit and activate distinct cellular subsets that perpetuate inflammation. This review provides an overview of the major cellular subpopulations and their intricate interactions within the RA synovium that ultimately lead to sustained synovial inflammation, bone erosion and cartilage damage. In addition, some insights into the potential disruption of such cellular activations and interactions as therapeutic strategies to achieve better treatment outcomes are also provided. • Activation of immune and non-immune cells plays key roles in RA onset and progression • Synovial changes form niches promoting pathogenic cellular behaviors in RA • Interactions among activated synovial cells drive persistent proinflammatory mediator secretion • Inflammatory mediators recruit/activate cellular subsets, sustaining joint inflammation in RA
Ganeshalingam et al. (Tue,) studied this question.