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I 型和 II 型干扰素可导致系统性红斑狼疮患者 B 细胞上趋化因子受体异常表达。

Type I and II interferons commit to abnormal expression of chemokine receptor on B cells in patients with systemic lupus erythematosus.

机构信息

The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan.

Mitsubishi Tanabe Pharma Corporation, UK.

出版信息

Clin Immunol. 2019 Mar;200:1-9. doi: 10.1016/j.clim.2018.12.017. Epub 2018 Dec 19.

DOI:10.1016/j.clim.2018.12.017
PMID:30576845
Abstract

Memory B cells are increased in systemic lupus erythematosus (SLE) cases, but the qualitative abnormalities and induction mechanism of these cells are unclear. Here, we subclassified B cells by their chemokine receptor expression and investigated their induction mechanism. The peripheral blood of patients with SLE showed higher levels of CXCR5 and CXCR3 B cells. CXCR5CXCR3 B cell levels were elevated in patients with active SLE, which decreased with improving disease conditions. Interferon (IFN)-γ stimulation increased CXCR3 expression, whereas IFN-β stimulation reduced CXCR5 expression in B cells. Furthermore, CXCR5CXCR3 B cells were induced by a combination of IFN-β and IFN-γ stimulation. Renal tissue examination of patients with active lupus nephritis confirmed the presence of CD19CXCR3 B cells. Collectively, the results revealed qualitative abnormalities accompanying reduced CXCR5 expression via type I IFN and enhanced CXCR3 expression via type II IFN in SLE, suggesting their involvement in B cell infiltration into tissues and inflammatory pathogenesis.

摘要

记忆 B 细胞在系统性红斑狼疮(SLE)患者中增加,但这些细胞的定性异常和诱导机制尚不清楚。在这里,我们根据趋化因子受体表达对 B 细胞进行了分类,并研究了它们的诱导机制。SLE 患者的外周血显示出更高水平的 CXCR5 和 CXCR3 B 细胞。活跃性 SLE 患者的 CXCR5CXCR3 B 细胞水平升高,随着病情的改善而降低。IFN-γ 刺激增加了 CXCR3 的表达,而 IFN-β 刺激减少了 B 细胞中 CXCR5 的表达。此外,IFN-β 和 IFN-γ 刺激的组合诱导了 CXCR5CXCR3 B 细胞。对活动性狼疮肾炎患者的肾组织检查证实了存在 CD19CXCR3 B 细胞。综上所述,结果表明,SLE 中通过 I 型 IFN 降低 CXCR5 表达和通过 II 型 IFN 增强 CXCR3 表达伴随着定性异常,提示它们参与了 B 细胞浸润到组织和炎症发病机制中。

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