Abstract / Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, progressive cartilage destruction, and bone erosion. Mouse models are essential for investigating RA pathogenesis, defining immune-cell and cytokine networks, and evaluating potential therapies. Common models include collagen-induced arthritis (CIA), collagen antibody-induced arthritis (CAIA), human TNF transgenic (hTNF-Tg) arthritis, and SKG arthritis, each representing distinct inflammatory mechanisms. CIA involves adaptive and innate immune cells, including CD4+ T cells, B cells, dendritic cells, macrophages, and neutrophils, with prominent roles for TNF-α, IL-1β, IL-6, IL-17A, GM-CSF, and IL-23. CAIA primarily reflects antibody-mediated and innate immune mechanisms involving neutrophils, macrophages, complement, and Fcγ receptors, with contributions from TNF-α, IL-1β, IL-6, GM-CSF, CXCL1, and CXCL2. The hTNF-Tg model highlights chronic TNF-driven inflammation involving macrophages and neutrophils and downstream inflammatory mediators such as IL-1β, IL-6, CXCL1, and CCL2. In contrast, the SKG model emphasizes autoreactive CD4+ T-cell and Th17 responses, with IL-17A, IL-6, and IL-23 contributing to arthritis following environmental stimulation. Collectively, these models are mechanistically complementary and provide distinct insights into immune activation, cytokine signaling, and joint pathology. However, differences in immune regulation, disease heterogeneity, and inflammatory mechanisms between mice and humans emphasize the importance of careful model selection and interpretation. This review summarizes major mouse models of RA, focusing on their immune-cell and inflammatory mediator networks, therapeutic applications, and translational relevance to human disease.