Extracellular matrices regulate extravasation journey of leukocytes and inflammatory tissue fate

Leukocyte extravasation across the blood endothelium to inflamed tissues is a crucial defence mechanism against invading pathogens. After the elimination of the pathogen in the tissue, inflammation needs to be resolved back to steady state. This cascade comprises at least three stages: transmigration through the endothelium and the underlying basement membrane, intra-tissue leukocyte activity, and tissue resolution. In each stage, extracellular matrix proteins in the vascular basement membrane and in tissues regulate a multitude of endothelial and leukocyte functions essential to completion of the cascade, either as a collective force-permissive structure or through signaling by individual matrix proteins. Proper orchestration of these diverse processes during the extravasation journey ensures effective defence and avoids development of chronic inflammatory diseases. This review will focus on how these extracellular matrices regulate the extravasation journey of leukocytes to illustrate their tight functional interdependence with profound impacts on the ultimate post-inflammation tissue fate.