CCN1/CYR61-mediated meticulous patrolling by Ly6C low monocytes fuels vascular inflammation

Significance Upon infection, circulating leukocytes leave the bloodstream and migrate into the inflammatory site. Neutrophils are the first leukocytes to be recruited within a few hours, followed by inflammatory lymphocyte antigen 6 complex (Ly6C)-positive monocytes. This study refines the model of the leukocyte recruitment cascade. We demonstrate that upon Toll-like receptor 7/8-mediated vascular inflammation, platelet activation drives the rapid mobilization of Ly6Clow monocytes to the luminal side of the endothelium. Accumulated Ly6Clow monocytes do not extravasate into the tissue. Instead, they meticulously patrol the endothelium and control the subsequent recruitment of neutrophils. Moreover, we show that endothelium-bound cyteine-rich protein 61 (CYR61)/CYR61 connective tissue growth factor nephroblastoma overexpressed 1 (CCN1) protein provides a molecular support for adequate patrolling of Ly6Clow monocytes in the steady state and under inflammatory conditions.