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

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.

Keywords

• dexd/h box helicase 60 (ddx60)|cyclic gmp-amp synthase (cgas)|type ⅰ interferon|systemic lupus erythematosus