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

doi:10.16352/j.issn.1001-6325.2024.07.0959

Abstract

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

CLC Number:

R392.3

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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