Guillermo Marcos-Zapatero, Dafne García-Mateos, Irene Carriles-Moar, Natalia Reglero-Real
Endothelial cells (ECs) are increasingly recognised as dynamic regulators of immunity rather than passive vascular barriers. By integrating inflammatory, metabolic, and mechanical cues, ECs actively shape leukocyte trafficking and determine inflammatory outcomes. Autophagy, a conserved lysosomal degradation pathway essential for cellular homeostasis, has emerged as a key determinant of endothelial function in health and disease. Recent work identifies EC autophagy as a context-dependent determinant of leukocyte trafficking, vascular inflammation, antigen presentation, and endothelial phagocytic capacity. Beyond controlling immune cell recruitment, EC autophagy intersects with xenophagy, efferocytosis, and vascular ageing, highlighting its broad immunomodulatory potential. In this review, we synthesise current evidence defining how autophagy within ECs regulates immune responses in a tissue-specific manner during acute and chronic inflammation. Collectively, these insights position EC autophagy as a central integrator of vascular and immune homeostasis and underscore its potential as a therapeutic target in chronic inflammatory and ageing-associated diseases.