Pathogenic and Regulatory Roles of Fibrinolytic Factors in Autoimmune Diseases

Autoimmune diseases arise from complex interactions of genetic, environmental, and hormonal factors, yet their precise causes remain elusive. Beyond its canonical role in fibrin degradation, the fibrinolytic system is increasingly recognized as both a pathogenic driver and a regulatory modulator in autoimmunity. Key factors-plasminogen (Plg), plasmin, α2-antiplasmin (α2AP), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1)-not only reflect secondary responses to vascular and immune dysregulation but also actively shape innate and adaptive immunity. They influence macrophage activation, dendritic cell maturation, T cell responses, and cytokine production, thereby bridging coagulation, inflammation, and tissue repair. This review integrates current evidence on the dual pathogenic and regulatory roles of fibrinolytic factors, organizing autoimmune diseases into systemic, organ-specific, and secondary syndromes. We further discuss how the imbalance of fibrinolysis can either promote inflammatory persistence or, conversely, facilitate resolution through fibrin clearance and immune homeostasis. By highlighting this bidirectional influence, the review aims to refine our understanding of fibrinolytic components as both contributors to and regulators of autoimmune disease pathogenesis.