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.

中性粒细胞从血液循环迁移到感染或损伤部位是关键的免疫反应，需要破坏排列在血管内部的内皮细胞 (EC)。不受管制的中性粒细胞跨内皮细胞迁移 (TEM) 是致病的，但其生理终止的分子基础仍然未知。在这里，我们证明了发炎组织中小静脉的 EC 表现出强烈的自噬反应，该反应在时间上与中性粒细胞运输的峰值一致，并且严格定位于 EC 接触。EC自噬的基因消融导致小鼠炎症模型中过度的中性粒细胞TEM和不受控制的白细胞迁移，而自噬的药理学诱导抑制中性粒细胞浸润到组织中。机械地，自噬调节 EC 连接的重塑和关键 EC 粘附分子的表达，促进它们的细胞内运输和降解。总的来说，我们已经确定自噬是 EC 白细胞运输机制的调节剂，旨在终止生理性炎症。