关键词: B cell CX3CR1 granzyme B systemic lupus erythematosus

来  源:   DOI:10.1093/jleuko/qiae127

Abstract:
As one molecule related to cytotoxicity, surface expression of C-X3-C motif receptor 1 (CX3CR1) was highly correlated with intracellular granzyme B (GZMB) in NK and cytolytic T cells. However, the expression of CX3CR1 and GZMB in B cells has not been clarified, and their clinical significance in systemic lupus erythematosus (SLE) remains unclear. This study aimed to clarify the changes and clinical significance of peripheral blood B cells expressing GZMB and/or CX3CR1 in SLE. Peripheral blood was collected from 39 SLE patients and 48 healthy controls. We found that GZMB and CX3CR1 expression varied in different B-cell subsets, with plasmablasts possessing the highest positive percentages, consistent with bioinformatics prediction. GZMB+ and CX3CR1+ percentages in circulating B cells and plasmablasts were increased in SLE patients. CX3CR1 was upregulated on B cells after in vitro stimulation. Notch intracellular domain (NICD) expression was significantly decreased in plasmablasts of SLE patients and CX3CR1 in plasmablasts was downregulated with the addition of JAG1. In conclusion, GZMB and CX3CR1 were increased in B cells and in plasmablasts of SLE patients and CX3CR1 was negatively regulated by Notch signal in plasmablasts, which may be involved in SLE pathogenesis.
摘要:
作为一个与细胞毒性相关的分子,C-X3-C基序受体1(CX3CR1)的表面表达与NK和溶细胞性T细胞中的细胞内粒酶B(GZMB)高度相关。然而,CX3CR1和GZMB在B细胞中的表达尚未明确,其在系统性红斑狼疮(SLE)中的临床意义尚不清楚。本研究旨在阐明SLE患者外周血B细胞表达GZMB和/或CX3CR1的变化及其临床意义。收集39例SLE患者和48例健康对照者的外周血。我们发现GZMB和CX3CR1的表达在不同的B细胞亚群中存在差异。浆细胞具有最高的阳性百分比,与生物信息学预测一致。SLE患者循环B细胞和成浆细胞中GZMB和CX3CR1的百分比增加。体外刺激后,CX3CR1在B细胞上上调。加入JAG1后,SLE患者的成浆细胞中Notch细胞内结构域(NICD)的表达显着降低,成浆细胞中的CX3CR1下调。总之,SLE患者的B细胞和浆细胞中GZMB和CX3CR1增加,浆细胞中CX3CR1受Notch信号负调控,这可能与SLE的发病机制有关。
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