Zhang Xin, Zou Mengjun, Liang Yue, Yang Yonghong, Jing Lina, Sun Minghui, Dong Zhilin, Zhang Xinyuan, Xiong Huabao, Dong Guanjun
Institute of Immunology and Molecular Medicine, Jining Medical University, Shandong, 272067, China; School of Medical Laboratory, Weifang Medical University, Shandong, 261053, China; Jining Key Laboratory of Immunology, Jining Medical University, Shandong, 272067, China.
Institute of Immunology and Molecular Medicine, Jining Medical University, Shandong, 272067, China; Jining Key Laboratory of Immunology, Jining Medical University, Shandong, 272067, China.
Eur J Pharmacol. 2022 Mar 15;919:174808. doi: 10.1016/j.ejphar.2022.174808. Epub 2022 Feb 10.
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.
Ⅰ型干扰素（IFN-Ⅰ）信号通路在生发中心B细胞分化及系统性红斑狼疮（SLE）发病机制中起关键作用。因此，靶向IFN-Ⅰ信号通路可作为SLE的一种有效治疗策略。牛蒡子苷元是牛蒡种子中的一种活性成分。据报道，它可作为炎症反应的负调节因子。然而，牛蒡子苷元在IFN-Ⅰ介导的生发中心B细胞分化调控过程及SLE发病机制中的作用尚不清楚。在本研究中，我们证明牛蒡子苷元可缓解MRL/lpr小鼠的自发性狼疮进展及咪喹莫特诱导的狼疮小鼠模型的病情。特别是，牛蒡子苷元显著降低了狼疮易感小鼠生发中心B细胞（7.1%，vs. 5.12%，p < 0.01）、滤泡辅助性T细胞（11.49%，vs. 5.53%，p < 0.05）和浆细胞（2.44%，vs. 1.39%，p < 0.01）的比例。体外研究表明，牛蒡子苷元通过激活蛋白磷酸酶2A（PP2A），在小鼠B细胞中显著抑制IFN-α诱导的CD69和干扰素刺激基因（ISG）表达以及JAK1和STAT1磷酸化，抑制率近减半。总体而言，这些数据突出了牛蒡子苷元在调节IFN-Ⅰ介导的生发中心B细胞分化及SLE发病机制中的作用。因此，牛蒡子苷元可能作为治疗SLE的潜在有效治疗靶点。
