Zhang Xiang, Hu Shouci, Luo Puchang, Li Zhiyu, Chen Zhejun, Xia Cong, Fan Linxuan, Li Rongqun, Chen Hongbo
Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, Zhejiang, PR China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease, Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology, Hangzhou 310006, Zhejiang, PR China.
Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, Zhejiang, PR China.
Immunol Lett. 2025 Jun;273:106993. doi: 10.1016/j.imlet.2025.106993. Epub 2025 Feb 27.
The development of systemic lupus erythematosus (SLE) involves both genetic and environmental factors. Epstein-Barr virus (EBV) infection has been implicated in SLE pathogenesis, particularly through the activity of latent membrane protein 1 (LMP-1). This study aimed to explore the role of LMP-1 in regulating susceptibility gene expression in SLE. Peripheral blood mononuclear cells (PBMCs) from SLE patients and H9 T cells were used to investigate this mechanism both in vivo and in vitro. RNA-seq analysis revealed that LMP-1 and the SLE susceptibility gene AT-rich interactive domain 5B (ARID5B) were significantly upregulated in SLE. Overexpression of LMP-1 in H9 T cells further increased ARID5B expression. Histone H3K27 methylation, catalyzed by enhancer of zeste homolog 2 (EZH2), was significantly elevated, suggesting epigenetic modifications play a role in this regulation. H3K27 methylation was studied due to its known involvement in transcriptional repression and chromatin remodeling in autoimmune diseases. Furthermore, phosphorylated p65 (p-p65), a marker of nuclear factor-kappa-B (NF-κB) pathway activation, was increased. Blocking the NF-κB signaling pathway reduced ARID5B expression, indicating that LMP-1 may regulate susceptibility genes through NF-κB signaling and histone modifications. These findings suggest that EBV LMP-1 contributes to SLE pathogenesis by epigenetically modulating susceptibility gene expression and activating inflammatory pathways.
系统性红斑狼疮（SLE）的发病涉及遗传和环境因素。爱泼斯坦-巴尔病毒（EBV）感染与SLE发病机制有关，尤其是通过潜伏膜蛋白1（LMP-1）的活性。本研究旨在探讨LMP-1在调节SLE易感性基因表达中的作用。使用SLE患者的外周血单核细胞（PBMC）和H9 T细胞在体内和体外研究这一机制。RNA测序分析显示，LMP-1和SLE易感基因富含AT的相互作用结构域5B（ARID5B）在SLE中显著上调。LMP-1在H9 T细胞中的过表达进一步增加了ARID5B的表达。由zeste同源物2增强子（EZH2）催化的组蛋白H3K27甲基化显著升高，表明表观遗传修饰在这一调节中起作用。由于已知H3K27甲基化参与自身免疫性疾病中的转录抑制和染色质重塑，因此对其进行了研究。此外，核因子-κB（NF-κB）信号通路激活的标志物磷酸化p65（p-p65）增加。阻断NF-κB信号通路可降低ARID5B的表达，表明LMP-1可能通过NF-κB信号通路和组蛋白修饰来调节易感基因。这些发现表明，EBV LMP-1通过表观遗传调节易感基因表达和激活炎症通路，促进了SLE的发病机制。
