This study examined how CD177+ neutrophils (PMNs) drive endothelial dysfunction in Behçet disease (BD), a chronic systemic vasculitis, by analyzing peripheral blood (n=38) and vascular tissue samples, performing RNA sequencing (n=7 for CD177+PMN), and using in vitro vascular endothelial cell (VEC) stimulation with BD-derived neutrophil extracellular traps (NETs).
CD177+PMNs were expanded in active/severe BD and accumulated in aortic walls; their NETs — enriched with histone H3.1 — induced endothelial senescence, SASP (↑IL-6, CXCL8, ICAM-1, p21, SA-β-gal, cell proliferation arrest), and PMN chemotaxis via TLR4 signaling, all of which were attenuated by senolytics.
Small RNA-sequencing cohort (n=7) limits statistical power; in vitro VEC stimulation may not fully replicate in vivo vascular complexity; causality in humans is inferred, not directly demonstrated.
CD177+PMN-derived NET components, particularly H3.1, may represent novel therapeutic targets in BD vasculitis; senolytic agents warrant further investigation as a potential strategy to break the senescence-inflammation cycle in BD vascular disease.
