The extracellular matrix as a critical mediator of immune reponses. The ECM serves as a rich source of cytokines, growth factors, and other bioactive degradation products (matrikines) that modulate immune responses to various pathological contexts. Matrix proteases, including MMP and ADAMTS enzymes, release cytokines/growth factors sequestered in the ECM and are capable of degrading ECM proteins to produce matrikines that influence immune cell migration and cytokine production. Signals provided by growth factors and matrikines to immune cells are critical for maintaining tissue homeostasis and in response to injury in a wide range of pathological contexts, including viral infection and cancer.