The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response
and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated
neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological
termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a
robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was
strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling
of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and
degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery
aimed at terminating physiological inflammation