Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients
Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients
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I 型干扰素促进系统性红斑狼疮患者移行 B 细胞的存活和促炎特性
DOI：
10.1038/s41423-018-0010-6
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发表时间：
2019-04-01
影响因子：
24.1
通讯作者：
Zhang, Xiaoming
中科院分区：
文献类型：
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作者：
Liu, Mei;Guo, Qiang;Zhang, Xiaoming
系统性红斑狼疮（SLE）的一个特征是B细胞耐受性被打破，并产生高亲和力自身抗体；然而，SLE中B细胞区室不依赖抗体的特性了解较少。在本研究中，我们对中国新发病SLE患者队列中的B细胞亚群及其促炎特性进行了广泛研究。我们观察到，与健康供体和类风湿关节炎患者相比，SLE患者的过渡型B细胞频率增加。SLE患者的血浆以I型干扰素依赖的方式有力地促进了过渡型B细胞的存活，这可通过直接用干扰素-α治疗来重现。此外，干扰素-α对过渡型B细胞存活增强的作用与NF -κB通路激活以及促凋亡分子Bax表达降低有关。SLE患者的过渡型B细胞具有更高的产生促炎细胞因子白细胞介素 - 6（IL - 6）的能力，这也与过度激活的I型干扰素通路有关。此外，产生IL - 6的过渡型B细胞的频率与SLE患者的疾病活动呈正相关，并且在短期标准治疗后这些细胞显著减少。因此，本研究在I型干扰素通路过度激活与活动性SLE患者中过渡型B细胞异常高的频率及其促炎特性之间建立了直接联系，这有助于理解I型干扰素和B细胞在SLE发病机制中的作用。
A hallmark of systemic lupus erythematosus (SLE) is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies; however, the antibody-independent features of the B-cell compartment in SLE are less understood. In this study, we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients. We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients. Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner, which can be recapitulated by direct IFN-α treatment. Furthermore, the effect of IFN-α on enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax. Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6, which was also linked to the overactivated type I IFN pathway. In addition, the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients, and these cells were significantly reduced after short-term standard therapies. Thus, the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients, which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.