1. Academic Validation
  2. Artesunate alleviates Sjögren's Syndrome by inhibiting the interferon-α signaling in plasmacytoid dendritic cells via TLR-MyD88-IRF7

Artesunate alleviates Sjögren's Syndrome by inhibiting the interferon-α signaling in plasmacytoid dendritic cells via TLR-MyD88-IRF7

  • Biomed Pharmacother. 2024 Jun 14:177:116885. doi: 10.1016/j.biopha.2024.116885.
Panpan Zhou 1 Mengxi Huang 1 Yang Hang 2 Sha Liu 1 Genhong Yao 2 Xiaojun Tang 2 Nan Xia 3 Lingyun Sun 4
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China.
  • 2 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China.
  • 3 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China. Electronic address: lindananxia@gmail.com.
  • 4 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China; Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China. Electronic address: lingyunsun@nju.edu.cn.
Abstract

Sjögren's syndrome (SS) is an autoimmune disease in which the salivary glands (SGs) and the lacrimal glands (LGs) are affected by lymphocytic infiltration and inflammation. It has been reported that interferon-α (IFN-α) released by plasmacytoid dendritic cells (pDCs) contribute to the pathology of SS, and ART has been shown to effectively ameliorates SS. Despite the current research endeavors, the mechanism of how ART works in the treatment of SS remains to be fully elucidated. Whether ART can treat SS by inhibiting IFN-α remains unclear. This hypothesis was tested both in vivo and in vitro settings during the study. The SS model mice, which were treated with ART, showed amelioration in symptoms related to dryness. RNA-seq analysis revealed strong anti-IFN-α signaling response upon ART treatment. Additional in vitro studies provided further confirmation that the application of ART inhibits the MyD88 protein expression and the nuclear translocation of IRF7. This suggests that the intervention of ART in the TLR-MyD88-IRF7 pathway plays a role in the therapeutic approach for SS. In summary, this study highlighted the therapeutic potential of ART in SS and ART inhibited the IFN-α signaling in pDCs via the TLR-MyD88-IRF7 pathway.

Keywords

Sjögren's Syndrome; artesunate; interferon-α; plasmacytoid dendritic cell.

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