Towards integrating extracellular matrix and immunological pathways

Abstract

The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM. We highlight studies that have taken an integrative approach to studying immune responses in the context of the ECM and studies that use novel proteomic strategies. Finally, we discuss research challenges relevant to the integration of immune and ECM networks and propose experimental and translational approaches to resolve these issues.

Keywords: Extracellular matrix; Immunology; Matrikines; Matrix metalloproteinases; Tissue remodeling.

Figure 1

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.