{"title":"系统性红斑狼疮患者循环浆细胞中颗粒酶 B 和 C-X3-C motif 受体 1 的上调受 Notch 信号的负调控。","authors":"Zhonghui Zhang, Zihang Yuan, Yiying Wang, Ya-Hui Zhang, Qi Li, Xingyue Zeng, Zhao Guan, Ayibaota Bahabayi, Pingzhang Wang, Chen Liu","doi":"10.1093/jleuko/qiae127","DOIUrl":null,"url":null,"abstract":"<p><p>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 natural killer 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 patients with SLE 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 patients with SLE. CX3CR1 was upregulated on B cells after in vitro stimulation. Notch intracellular domain expression was significantly decreased in plasmablasts of patients with SLE, 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 patients with SLE and CX3CR1 was negatively regulated by Notch signal in plasmablasts, which may be involved in SLE pathogenesis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1061-1071"},"PeriodicalIF":3.6000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Upregulation of granzyme B and C-X3-C motif receptor 1 in circulating plasmablasts was negatively regulated by Notch signal in patients with systemic lupus erythematosus.\",\"authors\":\"Zhonghui Zhang, Zihang Yuan, Yiying Wang, Ya-Hui Zhang, Qi Li, Xingyue Zeng, Zhao Guan, Ayibaota Bahabayi, Pingzhang Wang, Chen Liu\",\"doi\":\"10.1093/jleuko/qiae127\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 natural killer 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 patients with SLE 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 patients with SLE. CX3CR1 was upregulated on B cells after in vitro stimulation. Notch intracellular domain expression was significantly decreased in plasmablasts of patients with SLE, 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 patients with SLE and CX3CR1 was negatively regulated by Notch signal in plasmablasts, which may be involved in SLE pathogenesis.</p>\",\"PeriodicalId\":16186,\"journal\":{\"name\":\"Journal of Leukocyte Biology\",\"volume\":\" \",\"pages\":\"1061-1071\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Leukocyte Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/jleuko/qiae127\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Leukocyte Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jleuko/qiae127","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
作为一种与细胞毒性相关的分子,C-X3-C 矩阵受体 1(CX3CR1)的表面表达与 NK 细胞和细胞溶解性 T 细胞的细胞内颗粒酶 B(GZMB)高度相关。然而,CX3CR1和GZMB在B细胞中的表达尚未明确,它们在系统性红斑狼疮(SLE)中的临床意义也尚不清楚。本研究旨在阐明系统性红斑狼疮患者外周血B细胞表达GZMB和/或CX3CR1的变化及其临床意义。我们采集了 39 名系统性红斑狼疮患者和 48 名健康对照者的外周血。我们发现,GZMB和CX3CR1的表达在不同的B细胞亚群中有所不同,浆细胞的阳性率最高,这与生物信息学的预测一致。在系统性红斑狼疮患者中,循环B细胞和浆细胞中GZMB+和CX3CR1+的比例增加。体外刺激后,B 细胞的 CX3CR1 上调。系统性红斑狼疮患者浆细胞中的Notch胞内结构域(NICD)表达明显减少,加入JAG1后浆细胞中的CX3CR1被下调。总之,GZMB和CX3CR1在系统性红斑狼疮患者的B细胞和浆细胞中增加,CX3CR1在浆细胞中受Notch信号的负调控,这可能与系统性红斑狼疮的发病机制有关。
Upregulation of granzyme B and C-X3-C motif receptor 1 in circulating plasmablasts was negatively regulated by Notch signal in patients with systemic lupus erythematosus.
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 natural killer 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 patients with SLE 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 patients with SLE. CX3CR1 was upregulated on B cells after in vitro stimulation. Notch intracellular domain expression was significantly decreased in plasmablasts of patients with SLE, 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 patients with SLE and CX3CR1 was negatively regulated by Notch signal in plasmablasts, which may be involved in SLE pathogenesis.
期刊介绍:
JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.