Arctigenin inhibits abnormal germinal center reactions and attenuates murine lupus by inhibiting IFN-I pathway

Xin Zhang, Mengjun Zou, Yue Liang, Yonghong Yang, Lina Jing, Minghui Sun, Zhilin Dong, Xinyuan Zhang, Huabao Xiong, Guanjun Dong

Research output: Contribution to journalArticlepeer-review

Abstract

Interferon-I (IFN-I) signaling pathway plays a vital role in the differentiation of germinal center B cells and the pathogenesis of systemic lupus erythematosus (SLE). Therefore, targeting the IFN-I signaling pathway could serve as an effective treatment strategy in SLE. Arctigenin is an active ingredient present in the seeds of Arctium lappa L. It has been reported to act as a negative regulator of inflammatory responses. However, the role of arctigenin remains unknown in the regulation process of the IFN-I-mediated differentiation of germinal center B cells and the pathogenesis of SLE. In the present study, we demonstrated that arctigenin alleviated the progression of spontaneous lupus in MRL/lpr mice and imiquimod-mediated lupus mice. Especially, arctigenin significantly reduced the proportions of germinal center B cells (7.1%, vs. 5.12%, p < 0.01), follicular helper T cells (11.49%, vs. 5.53%, p < 0.05), and plasma cells (2.44%, vs. 1.39%, p < 0.01) in the lupus-prone mice. In vitro studies have shown that arctigenin significantly inhibited the IFN-α-induced CD69 and interferon-stimulated gene (ISG) expressions along with the phosphorylation of JAK1 and STAT1 by nearly half in murine B cells via activating PP2A. Overall, these data highlighted the role of arctigenin in regulating the IFN-I-mediated differentiation of germinal center B cells and the pathogenesis of SLE. Thus, arctigenin may be used as a potentially effective therapeutic target for the treatment of SLE.

Original languageEnglish
Article number174808
JournalEuropean Journal of Pharmacology
Volume919
DOIs
StatePublished - 15 Mar 2022
Externally publishedYes

Keywords

  • Arctigenin
  • B cell
  • Germinal center
  • IFN-α
  • SLE

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