Regulation of neutrophil function by the extracellular matrix

Neutrophils play a critical role in maintaining healthy tissue by acting as the first cellular responders to inflammatory challenges. Unfortunately, when this response is dysregulated, defects in neutrophil function can contribute to the pathogenesis of several diseases and conditions, including cancer, fibrosis, and aberrant wound healing. Understanding the factors that regulate the neutrophil response is critical for improving disease outcomes. It is becoming increasingly appreciated that the extracellular matrix (ECM) serves as a significant regulator of the neutrophil response. The ECM is a complex network of fibrous proteins and proteoglycans that provides both physical and biochemical cues that can modulate cell behavior. Importantly, the composition, structure, and mechanics of the ECM often undergo significant changes in disease. Studies have shown that matrix stiffness and composition can alter neutrophil behavior, but our understanding of how the various structural and mechanical properties of the ECM govern the neutrophil response remains incomplete. In part, this is due to the challenges involved in isolating distinct properties of the matrix to determine their individual roles in regulating the neutrophil response. In this review, we summarize the recent efforts that have been made to better understand how ECM properties affect the neutrophil inflammatory response and offer suggestions for future directions for the field.