2. Academic Validation
  3. The potential roles of type I interferon activated neutrophils and neutrophil extracellular traps (NETs) in the pathogenesis of primary Sjögren's syndrome

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

  • Arthritis Res Ther. 2022 Jul 19;24(1):170. doi: 10.1186/s13075-022-02860-4.
Yu Peng  # 1,  Xunyao Wu  # 2,  Shulan Zhang  # 1,  Chuiwen Deng 1,  Lidan Zhao 1,  Mu Wang 3,  Qingjun Wu 1,  Huaxia Yang 1,  Jiaxin Zhou 1,  Linyi Peng 1,  Xuan Luo 1,  Yingying Chen 1,  Anqi Wang 1,  Qiufeng Xiao 1,  Wen Zhang 1,  Yan Zhao 1,  Xiaofeng Zeng 1,  Yunyun Fei 4
Affiliations

Affiliations

  • 1 Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, #1 Shuai-Fu-Yuan, Dongcheng District, Beijing, 100730, China.
  • 2 Clinical Biobank, Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 3 Department of Stomatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China.
  • 4 Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, #1 Shuai-Fu-Yuan, Dongcheng District, Beijing, 100730, China. [email protected].
  • # Contributed equally.
PMID: 35854322 DOI: 10.1186/s13075-022-02860-4
Abstract

Objective: Neutrophils and aberrant NETosis have been implicated in the pathogenesis of diverse autoimmune diseases; however, their roles in primary Sjögren'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-α 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.

Keywords

Mitochondrial damage; Neutrophil extracellular traps; Neutrophils; Primary Sjögren’s syndrome; Type I interferon.

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