DDX60促进系统性红斑狼疮患者PBMCs中Ⅰ型干扰素的表达  

DDX60 promotes expression of typeⅠinterferon in PBMCs from patients with systemic lupus erythematosus

作　　者：袁勋 王宇扬 孟姝[1] YUAN Xun;WANG Yuyang;MENG Shu(Department of Immunology,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005,China)

机构地区：[1]中国医学科学院基础医学研究所,北京协和医学院基础学院免疫学系,北京100005

出　　处：《基础医学与临床》2024年第7期959-964,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(82171726)。

摘　　要：目的探究DExD/H盒解旋酶60(DDX60)通过调控dsDNA-cGAS-IFN-Ⅰ通路对系统性红斑狼疮(SLE)进展的作用机制。方法通过分析RNA测序数据集发现DDX60 mRNA水平在SLE患者和健康人外周血单个核细胞(PBMCs)中的差异。分析SLE患者PBMCs的DDX60 mRNA水平与疾病活动度的相关关系。通过α干扰素(IFN-α)刺激人源单核细胞系THP-1,明确DDX60是否为干扰素诱导基因(ISG)。通过沉默和敲除DDX60,再转染双链DNA(dsDNA)poly(dA:dT),利用RT-qPCR检测β1干扰素(IFNB1)的mRNA水平。结果RNA测序数据集和RT-qPCR结果表明DDX60在SLE患者PBMCs中高表达。相关性分析表明,SLE患者PBMCs的DDX60 mRNA水平与疾病活动度呈正相关关系。IFN-α可以诱导THP-1细胞表达DDX60,表明DDX60是ISG。沉默DDX60后,poly(dA:dT)诱导的IFNB1 mRNA水平显著降低。结论DDX60在SLE患者PBMCs中高表达,IFN-Ⅰ-DDX60-dsDNA-cGAS-IFN-Ⅰ正反馈通路参与SLE进展,可能成为SLE临床诊治的靶点,具有诊断及预后评估价值。Objective To explore the role of DExD/H box helicase 60(DDX60)in the development of systemic lu⁃pus erythematosus(SLE)by regulating the dsDNA⁃cGAS⁃IFN⁃Ⅰpathway.Methods Differences in DDX60 mRNA level in peripheral blood mononuclear cells(PBMCs)from SLE patients and healthy people were examined by analyzing RNA sequencing data and verified by RT⁃qPCR.The correlation between DDX60 mRNA level in PBMCs and disease activity of SLE patients was analyzed.Whether DDX60 was an interferon⁃stimulated gene(ISG)was clarified by interferon⁃alpha(IFN⁃α)stimulation of human acute monocyte leukemia cell line THP⁃1.The mRNA level of interferon⁃beta1(IFNB1)was detected by RT⁃qPCR after silencing and knockdown of DDX60 and followed by double⁃stranded DNA(dsDNA)poly(dA:dT)transfection.Results RNA sequencing data and RT⁃qPCR result found high expression of DDX60 in PBMCs of SLE patients.DDX60 mRNA level in PBMCs was positively correlated with disease activity of SLE patients.IFN⁃αinduced THP⁃1 cells to express DDX60,suggesting that DDX60 was an ISG.Silencing DDX60 resulted in a decrease in poly(dA:dT)⁃induced IFNB1 mRNA level.Conclusions DDX60 is highly expressed in PBMCs of SLE patients and involved in the development of SLE through the positive feedback loop of IFN⁃Ⅰ⁃DDX60⁃dsDNA⁃cGAS⁃IFN⁃Ⅰ,which suggests that DDX60 may be a target for the clinical diagnosis and treatment of SLE.The result of this research may support diagnosis and progno⁃sis evaluation of SLE patients.

关 键 词：DExD/H盒解旋酶60(DDX60) 环鸟苷酸-腺苷酸合成酶(cGAS) Ⅰ型干扰素 系统性红斑狼疮 

分 类 号：R392.3[医药卫生—免疫学]