Endothelial cell autophagy keeps neutrophil trafficking under control.

A defining feature of an inflammatory reaction is infiltration of neutrophils into tissues, a response that requires breaching of endothelial cells (ECs) that line the lumenal aspect of blood vessels. Dysregulated neutrophil trafficking is a hallmark of pathology, but details of the molecular mechanisms that terminate neutrophil breaching of venular walls remain unclear. In this work, we have identified EC autophagy as a negative regulator of neutrophil diapedesis in acute physiological inflammation. Specifically, in vivo, inflamed venular ECs upregulate autophagy, a response that is selectively localized to EC contacts and temporally aligned with the peak of neutrophil trafficking. Genetic ablation of EC autophagy leads to excessive neutrophil tissue infiltration in multiple inflammatory models and supports enhanced neutrophil transendothelial migration (TEM), while pharmacological induction of autophagy inhibits neutrophil migration. Mechanistically, autophagy machinery regulates the architecture of EC contacts and controls the reorganization and degradation of adhesion molecules, constituting a physiological brake on leukocyte trafficking.