ARD: 免疫细胞多组学分析揭示了氧化磷酸化对狼疮 B 细胞功能和器官损伤的作用

2022-03-14 MedSci原创 MedSci原创

研究者确定了一种OXPHOS调节基因PRDX6(过氧化还原蛋白 6)作为 SLE B 细胞的关键驱动因素。

     目的:系统性红斑狼疮(SLE)是典型的系统性自身免疫性疾病。虽然长期预后已大大改善,但仍需要更好的长期生存率。 I 型干扰素 (IFN) SLE的一个突出特征,然而它不是理想的治疗靶点或结果预测因子。为了更准确地探索 SLE 的免疫通路,研究者使用来自外周血的19个免疫细胞亚群进行了转录组、表观基因组和基因组分析。

     方法:研究者对 19 个免疫细胞亚群进行分类,鉴定了 107 SLE 患者和 92 名健康对照者的 mRNA 表达谱和遗传多态性。结合差异表达基因和表达数量性状位点分析,寻找SLE发病机制中的关键驱动基因。

      结果:研究者发现了 SLE 记忆 B 细胞中氧化磷酸化 (OXPHOS)/线粒体功能障碍的转录组学、表观遗传和遗传学的重要性。尤其是研究者确定了一种OXPHOS调节基因PRDX6(过氧化还原蛋白 6)作为 SLE B 细胞的关键驱动因素Prdx6缺陷B细胞显示上调线粒体呼吸以及抗体产生。OXPHOS 特征与SLE记忆B细胞中的IIFN 信号相关基因 (ISRGs) 特征相关。此外,ISRGs 中与先天免疫信号相关的基因组与 OXPHOS 相关,这两个特征显示与 SLE 器官损伤以及特定临床表型相关。

      结论:这项工作阐明了系统性红斑狼疮的潜在预后标志物。由于 OXPHOS 由电子传递链(线粒体中的一个功能单元)组成,这些发现表明线粒体功能障碍作为参与SLE的关键免疫途径的重要性。

 

出处:Takeshima Y, Iwasaki Y, Nakano M, et al.Immune cell multiomics analysis reveals contribution of oxidative phosphorylation to B-cell functions and organ damage of lupus. Annals of the Rheumatic Diseases Published Online First: 02 March 2022. doi: 10.1136/annrheumdis-2021-221464

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