In their report, Chen et al. provide new insights into psoriasis pathogenesis, showing that neutrophil infiltration of skin lesions increases vascular endothelial cell (VEC) activation, leading to cutaneous vasodilation and enhanced vascular permeability. In patients with psoriasis, neutrophil-derived matrix metalloproteinase 9 (MMP-9) plays a pivotal role in VEC barrier dysfunction, via extracellular signal-regulated kinase-1/2 and p38 pathways. Pharmacologic inhibition of MMP-9 in two different models confers reduced cutaneous vasodilation, vascular permeability, and inflammation, suggesting MMP-9 as a target in psoriasis pathogenesis.