Arthritis & rheumatology (Hoboken, N.J.) · 2026
CD177+ Neutrophils Promote Endothelial Senescence Through Extracellular Traps in Behçet Disease.
СтатьяНазвание и аннотация: Перевод в очереди
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Wang Xiaoou, Yu Xin, Wang Xun, Sun Luxi, Zhang Menghao, Wang Zhimian, Liu Yeling, Ao Yiyuan, Wu Jingwen, Wang Wenze, Liu Jinjing, Chen Hua, Zheng Wenjie
Аннотация
OBJECTIVE: To investigate CD177+PMN dysregulation on endothelial cells in Behçet disease (BD), a chronic systemic vasculitis characterized by polymorphonuclear neutrophil (PMN) activation and endothelial dysfunction.
METHODS: We reanalyzed BD PMN RNA-sequencing data and quantified CD177+PMN in BD peripheral (n = 38) and vascular tissue. We then analyzed BD and healthy control CD177+PMN using RNA sequencing (n = 7) and measured neutrophil extracellular trap (NET) production, which were used to stimulate vascular endothelial cells (VECs) for RNA-sequencing analysis. Differentially expressed proteins in NETs were determined by mass spectrometry. Senescence, senescence-associated secretory phenotype (SASP), and PMN chemotaxis of VECs treated with BD CD177+PMN-derived NETs were assessed.
RESULTS: Transcriptome analysis revealed BD PMN overexpressed CD177. CD177+PMN subset was expanded in active and severe systemic BD and accumulated in BD aortic walls. Enhanced NETosis and oxidative phosphorylation in BD CD177+PMN were noted in RNA sequencing, which were confirmed in both resting and activated BD CD177+PMN. BD CD177+PMN-derived NETs promoted senescence, SASP, and PMN chemotaxis in VECs using RNA-sequencing analysis, which were validated by up-regulated IL-6, CXCL8, ICAM-1, p21, SA-β-gal, and cell proliferation arrest. Mass spectrometry identified that BD CD177+PMN-derived NETs contained more histone 3.1 (H3.1). H3.1 induced senescence, SASP, and PMN chemotaxis in VECs via Toll-like receptor 4 signaling, which was attenuated by senolytics.
CONCLUSION: Increased CD177+PMN in patients with BD promotes senescence and SASP in VECs through secreting H3.1-enriched NETs, which recruit PMN and collectively contribute to vasculitis in BD.
METHODS: We reanalyzed BD PMN RNA-sequencing data and quantified CD177+PMN in BD peripheral (n = 38) and vascular tissue. We then analyzed BD and healthy control CD177+PMN using RNA sequencing (n = 7) and measured neutrophil extracellular trap (NET) production, which were used to stimulate vascular endothelial cells (VECs) for RNA-sequencing analysis. Differentially expressed proteins in NETs were determined by mass spectrometry. Senescence, senescence-associated secretory phenotype (SASP), and PMN chemotaxis of VECs treated with BD CD177+PMN-derived NETs were assessed.
RESULTS: Transcriptome analysis revealed BD PMN overexpressed CD177. CD177+PMN subset was expanded in active and severe systemic BD and accumulated in BD aortic walls. Enhanced NETosis and oxidative phosphorylation in BD CD177+PMN were noted in RNA sequencing, which were confirmed in both resting and activated BD CD177+PMN. BD CD177+PMN-derived NETs promoted senescence, SASP, and PMN chemotaxis in VECs using RNA-sequencing analysis, which were validated by up-regulated IL-6, CXCL8, ICAM-1, p21, SA-β-gal, and cell proliferation arrest. Mass spectrometry identified that BD CD177+PMN-derived NETs contained more histone 3.1 (H3.1). H3.1 induced senescence, SASP, and PMN chemotaxis in VECs via Toll-like receptor 4 signaling, which was attenuated by senolytics.
CONCLUSION: Increased CD177+PMN in patients with BD promotes senescence and SASP in VECs through secreting H3.1-enriched NETs, which recruit PMN and collectively contribute to vasculitis in BD.