DDX60 promotes expression of type Ⅰ interferon in PBMCs from patients with systemic lupus erythematosus
10.16352/j.issn.1001-6325.2024.07.0959
- VernacularTitle:DDX60促进系统性红斑狼疮患者PBMCs中Ⅰ型干扰素的表达
- Author:
Xun YUAN
1
;
Yuyang WANG
;
Shu MENG
Author Information
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
- Keywords:
DExD/H box helicase 60(DDX60);
cyclic GMP-AMP synthase(cGAS);
type Ⅰ interferon;
systemic lupus erythe-matosus
- From:
Basic & Clinical Medicine
2024;44(7):959-964
- CountryChina
- Language:Chinese
-
Abstract:
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-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 progno-sis evaluation of SLE patients.
