MicroRNA-98-5p Inhibits IFI44L-Mediated Differentiation of Dendritic Cells and Activation of Interferon Pathway in Systemic Lupus Erythematosus

ABSTRACT

MicroRNA-98-5p (miR-98-5p) plays a protective role in the pathogenesis of autoimmune diseases through anti-inflammatory effects, but little is known about its role in Systemic lupus erythematosus (SLE). Our previous study suggested Interferon-inducible 44 like (IFI44L) overexpressed in monocytes which contributes to the pathogenesis of SLE by enhancing the maturation and functions of monocyte-derived dendritic cells (Mo-DCs), and miR-98-5p can regulate the expression of IFI44L. In this study, we identified miR-98-5p lowly expressed in both peripheral blood mononuclear cells (PBMCs) and monocytes of SLE patients along with high expression of IFI44L. IFI44L serves as target gene of miR-98-5p which inhibits differentiation of Mo-DCs and IFI44L-mediated activation of interferon pathway. We further showed that miR-98-5p promotes methylation of the IFI44L promoter to down-regulate its expression in SLE. Our results reveal an important role for miR-98-5p in the IFI44L-mediated immune imbalance of SLE and suggest a potential therapeutic target for SLE in the future.

KEYWORDS:

• Interferon-inducible 44 like
• microRNA-98-5p
• monocyte
• monocyte-derived dendritic cell
• systemic lupus erythematosus

Acknowledgments

The authors thank Prof. Qianjin Lu, Prof. Ming Zhao, and Prof. Haijing Wu in Hunan Key Laboratory of Medical Epigenomics for their help and all students in Hunan Key Laboratory of Medical Epigenomics for their efforts to collect samples.

Authors’ contributions

X.H. conducted the statistical analysis, cell cultures, transfection, RNA isolation, real-time quantitative qRT-PCR, flow cytometric analysis, western blot, DNA methylation detection, and drafted the manuscript. Y.T., R.W., and Q.L. helped with the manuscript writing. S.L. designed the study, helped with statistical analyses, and revised the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/08820139.2023.2300346.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [Grant No. 81703133, Grant No. 82003364], the Natural Science Foundation of Hunan Province, China [Grant No. 2021JJ40856, Grant No. 2023JJ40827] and the Scientific Research Launch Project for new employees of The Second Xiangya Hospital of Central South University [No. 0007433].