DDX60促进系统性红斑狼疮患者PBMCs中Ⅰ型干扰素的表达

doi:10.16352/j.issn.1001-6325.2024.07.0959

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (7): 959-964.doi: 10.16352/j.issn.1001-6325.2024.07.0959

DDX60促进系统性红斑狼疮患者PBMCs中Ⅰ型干扰素的表达

袁勋, 王宇扬, 孟姝^*

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

收稿日期:2024-02-18 修回日期:2024-05-21 出版日期:2024-07-05 发布日期:2024-06-26
通讯作者: ^*mengshu129@163.com
基金资助:
国家自然科学基金(82171726)

DDX60 promotes expression of type Ⅰ interferon in PBMCs from patients with systemic lupus erythematosus

YUAN Xun, WANG Yuyang, MENG Shu^*

Department of Immunology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China

Received:2024-02-18 Revised:2024-05-21 Online:2024-07-05 Published:2024-06-26
Contact: ^*mengshu129@163.com

摘要/Abstract

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。

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

Abstract: Objective To explore the role of DExD/H box helicase 60(DDX60) in the development of systemic lupus erythematosus (SLE) by regulating the dsDNA-cGAS-IFN-Ⅰ pathway. 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-α induced 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 prognosis evaluation of SLE patients.

Key words: DExD/H box helicase 60 (DDX60), cyclic GMP-AMP synthase (cGAS), type Ⅰ interferon, systemic lupus erythematosus

中图分类号:

R392.3

袁勋, 王宇扬, 孟姝. DDX60促进系统性红斑狼疮患者PBMCs中Ⅰ型干扰素的表达[J]. 基础医学与临床, 2024, 44(7): 959-964.

YUAN Xun, WANG Yuyang, MENG Shu. DDX60 promotes expression of type Ⅰ interferon in PBMCs from patients with systemic lupus erythematosus[J]. Basic & Clinical Medicine, 2024, 44(7): 959-964.

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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 type Ⅰ interferon in PBMCs from patients with systemic lupus erythematosus

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