Chen Liying, Fang Ting, Yao Xinyi, Zhao Ting, Lu Dingqi, Wang Xinchang
The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
J Ethnopharmacol. 2025 Jun 12;349:119914. doi: 10.1016/j.jep.2025.119914. Epub 2025 May 1.
Jieduquyuziyin Prescription (JP) is an evidence-based herbal formula used to treat systemic lupus erythematosus (SLE). Its efficacy in reducing double-stranded DNA antibodies (dsDNA) has been confirmed by clinical trials and experiments. These results highlight the important value of maintenance of B cell immune homeostasis through integration of ethnopharmacology.
Extrafollicular effector B cell subsets are the primary source of dsDNA antibodies in SLE. This study investigated the mechanism of extrafollicular effector B cells in SLE treated by JP.
SLE, Sjögren's Syndrome (SS) patients and healthy controls (HCs) were assessed for double negative 2 B cells (DN2 B) using flow cytometry. Network pharmacology and GEO datasets identified stargets of JP and mechanisms on DN2 B cells. MRL/lpr mice were randomly divided into model (MOD), JP and prednisone (Pred) groups for evaluating level and function of extrafollicular effector B cells, with serum antibodies, cytokines, and renal function by enzyme-linked immunosorbent assay(ELISA) and renal pathology staining.. Transcriptome sequencing from sorted CD19B cells in spleen, flow cytometry and immunofluorescence were performed for detecting the B cell subsets frequency and spatial position. Furthermore, the effects of JP on extrafollicular effector B cell were assessed using transwell, real-time qPCR, Western blot and flow cytometry in resiquimod (R848) induced Raji cells.
DN2 B cells expanded in SLE patients and responded to treatment. Integrin αV (ITGAV) in B cells from SLE patients and mice shows potential as a therapeutic target after JP treatment. JP improved renal pathology and reduced levels of ABCs and ITGAV in the extrafollicular zone, alleviating tissue inflammation and antibody production in SLE by regulating extrafollicular effector B cells expressing ZEB2 and ITGAV.
JP alleviates tissue inflammation and antibody production in SLE by regulating extrafollicular effector B cells expressing integrin αV signaling, thus restoring immune homeostasis.
解毒祛瘀滋阴方（JP）是一种用于治疗系统性红斑狼疮（SLE）的循证草药配方。其在降低双链DNA抗体（dsDNA）方面的疗效已通过临床试验和实验得到证实。这些结果突出了通过整合民族药理学维持B细胞免疫稳态的重要价值。
滤泡外效应B细胞亚群是SLE中dsDNA抗体的主要来源。本研究探讨了JP治疗SLE时对滤泡外效应B细胞的作用机制。
采用流式细胞术评估系统性红斑狼疮（SLE）、干燥综合征（SS）患者及健康对照（HC）的双阴性2 B细胞（DN2 B）。通过网络药理学和GEO数据集确定JP的作用靶点及对DN2 B细胞的作用机制。将MRL/lpr小鼠随机分为模型（MOD）、JP和泼尼松（Pred）组，通过酶联免疫吸附测定（ELISA）和肾脏病理染色评估滤泡外效应B细胞的水平和功能、血清抗体、细胞因子及肾功能。对脾脏中分选的CD19+B细胞进行转录组测序、流式细胞术和免疫荧光检测，以确定B细胞亚群的频率和空间位置。此外，在瑞喹莫德（R848）诱导的Raji细胞中，采用Transwell、实时定量PCR、蛋白质免疫印迹法和流式细胞术评估JP对滤泡外效应B细胞的影响。
SLE患者的DN2 B细胞增多且对治疗有反应。SLE患者和小鼠B细胞中的整合素αV（ITGAV）在JP治疗后显示出作为治疗靶点的潜力。JP改善了肾脏病理，降低了滤泡外区ABC和ITGAV的水平，通过调节表达ZEB2和ITGAV的滤泡外效应B细胞减轻了SLE中的组织炎症和抗体产生。
JP通过调节表达整合素αV信号的滤泡外效应B细胞减轻SLE中的组织炎症和抗体产生，从而恢复免疫稳态。
