Figure 1.

Macrophage-induced immune-inflammatory injury and pathological fibrosis in musculoskeletal disorders. Macrophage phagocytic function is impaired in musculoskeletal disorders, thereby inhibiting the clearance of apoptotic cells. Increased apoptotic cells promote the production of autoantigens and antibodies, exacerbating inflammation. Moreover, macrophages promote the migration and abnormal activation of T cells, including increased Th1/Th17 differentiation and downregulated Treg differentiation, ultimately leading to B cell abnormal activation. Imbalance in M1/M2 macrophage ratio also participates in autoimmunity. Abnormal M1 macrophage activation promotes the production of pro-inflammatory cytokines, such as IL-6, iNOS, TNF-α, and IL-1β, thereby promoting inflammation in target organs. Reduced M2 polarization impairs the production of anti-inflammatory cytokines and immune tolerance. Additionally, M2 macrophage receptor-ligand interactions can also cause epithelial-to-mesenchymal transition (EMT) and fibrosis in autoimmune diseases (e.g., SSc).