The Extracellular Matrix and the Immune System in Acute Lung Injury: Partners in Damage and Repair

Acute lung injury (ALI) is driven by a complex interplay between immune dysregulation and structural matrix remodeling. Although inflammation, oxidative stress, and disturbances in the coagulation-fibrinolysis system have long been recognized as core pathogenic drivers, growing evidence demonstrates that the extracellular matrix (ECM) functions as an active regulator of lung injury and repair rather than a passive structural scaffold. This review synthesizes current advances in ECM biology and immunopathology to delineate how ECM remodeling influences, and is concurrently shaped by, the inflammatory microenvironment. We outline how biochemical and physical modes of ECM remodeling engage in bidirectional crosstalk with the immune system. Emerging therapeutic strategies targeting this ECM-immune axis are critically evaluated, including modulation of protease activity, interventions that reprogram cell-matrix interactions, and approaches that restore ECM integrity using stem cells or engineered biomaterials. By redefining ALI as a disease of immune-matrix reciprocity, this review underscores the ECM as both a structural framework and a dynamic immunoregulatory hub, providing conceptual and mechanistic insights that may guide the development of precision therapies for ALI and related pulmonary disorders.