Figure 1.

Schematic of components of the extracellular matrix (ECM) and their immunoregulatory role. The ECM participates in the control of the immune response with its structural and functional constituents through various mechanisms. Complement components (CC), cytokines/chemokines (CK) and immune cells are retained by the ECM meshwork or specifically bind to its structural components such as collagen, elastin, proteoglycans or glycosaminoglycans (GAG). This results in the local activity of immune regulators. Through turnover mechanisms involving extracellular proteases (e.g., MMPs or ADAMs), the ECM influences the transformation of proactive (pro-CK) to active CKs, thereby influencing their inflammatory and chemotactic function with consequent influence on the extravasation and migration of immune cells. Inhibitors of extracellular proteases, including the tissue inhibitor of metalloproteases 3 (TIMP3), further modulate immune regulation resulting from the digestion of the ECM and the inflammatory agents residing within. Matricellular proteins such as vitronectin (VTN) or tenascin-C (TN-C), which mediate the interaction between cells and their extracellular environment also influence ECM-associated immunological processes, including complement activation, immune cell migration, phagocytic removal of apoptotic cells, and secretion of inflammatory molecules.