The potential roles of type I interferon activated neutrophils and neutrophil extracellular traps (NETs) in the pathogenesis of primary Sjogren's syndrome

被引：50

作者：

Peng, Yu ^{[1
]}

Wu, Xunyao ^{[2
]}

Zhang, Shulan ^{[1
]}

Deng, Chuiwen ^{[1
]}

Zhao, Lidan ^{[1
]}

Wang, Mu ^{[3
]}

Wu, Qingjun ^{[1
]}

Yang, Huaxia ^{[1
]}

Zhou, Jiaxin ^{[1
]}

Peng, Linyi ^{[1
]}

Luo, Xuan ^{[1
]}

Chen, Yingying ^{[1
]}

Wang, Anqi ^{[1
]}

Xiao, Qiufeng ^{[1
]}

Zhang, Wen ^{[1
]}

Zhao, Yan ^{[1
]}

Zeng, Xiaofeng ^{[1
]}

Fei, Yunyun ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Dermatol & Immunol Dis, Peking Union Med Coll Hosp, State Key Lab Complex Severe & Rare Dis,Dept Rheu, 1 Shuai Fu Yuan, Beijing 100730, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Med Res Ctr, Clin Biobank, Beijing, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Stomatol, 1 Shuaifuyuan, Beijing 100730, Peoples R China

来源：

ARTHRITIS RESEARCH & THERAPY | 2022年 / 24卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Primary Sjogren's syndrome; Neutrophils; Neutrophil extracellular traps; Type I interferon; Mitochondrial damage; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; LOW-DENSITY GRANULOCYTES; NETTING NEUTROPHILS; LUPUS; CONTRIBUTE; THROMBOSIS; RELEASE; NETOSIS; CELLS; RISK;

D O I：

10.1186/s13075-022-02860-4

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective Neutrophils and aberrant NETosis have been implicated in the pathogenesis of diverse autoimmune diseases; however, their roles in primary Sjogren's syndrome (pSS) remain unclear. We aimed to reveal the potential roles of neutrophils and neutrophil extracellular traps (NETs) in pSS. Methods pSS patients were enrolled and NETosis markers were measured in plasma and labial glands using ELISA and immunofluorescence. The gene signatures of neutrophils were assessed by RNA-Seq and RT-PCR. Reactive oxygen species (ROS), mitochondrial ROS (MitoSOX) production, and JC-1 were measured by flow cytometry. Results NETosis markers including cell-free DNA (cf-DNA) and myeloperoxidase (MPO) in plasma and labial glands from pSS patients were significantly higher than healthy controls (HCs) and were associated with disease activity. RNA sequencing and RT-qPCR revealed activated type I IFN signaling pathway and higher expression of genes related to type I interferon in pSS neutrophils. Further stimulating with IFN-alpha 2a in vitro significantly induced ROS production and JC-1 monomer percentage in pSS neutrophils. Conclusions Our data suggest the involvement of neutrophils and enhanced NETosis in pSS patients. Further mechanism study in vitro revealed that type I IFN activation in pSS neutrophils led to mitochondrial damage and related ROS production which finally result in the generation of NETs.

引用

页数：13

共 41 条

[21] Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease [J].