Elevated expression of miR-142-3p is related to the pro-inflammatory function of monocyte-derived dendritic cells in SLE

• Published in: Arthritis research & therapy Vol. 18; no. 1; p. 263
• Main Authors: Wang, Yilun, Liang, Jun, Qin, Haihong, Ge, Yan, Du, Juan, Lin, Jinran, Zhu, Xiaohua, Wang, Jie, Xu, Jinhua
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.11.2016; BioMed Central
• Subjects: Adolescent; Adult; Arthritis; CD4-Positive T-Lymphocytes - immunology; Coculture Techniques; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Development and progression; Female; Flow Cytometry; Gene Expression Profiling; Genetic aspects; Humans; Inflammation - genetics; Inflammation - immunology; Inflammation - metabolism; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lymphocyte Activation - immunology; MicroRNA; MicroRNAs - biosynthesis; MicroRNAs - immunology; Middle Aged; Monocytes - cytology; Monocytes - immunology; Monocytes - metabolism; Oligonucleotide Array Sequence Analysis; Physiological aspects; Real-Time Polymerase Chain Reaction; Systemic lupus erythematosus; Transcriptome; Young Adult; China; Monocyte-derived DCs; SLE; MicroRNA
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-016-1158-z

Recent studies have shown that alterations in the function of dendritic cells (DCs) are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanism of the alteration remains unclear. We cultured monocyte-derived DCs (moDCs) in vitro and examined the cytokines and chemokines in the supernatants of moDCs in negative controls (NC) and SLE patients in active phase. We then profiled microRNAs (miRNAs) of LPS-stimulated moDCs in SLE patients and used real-time PCR to verify the differentially expressed miRNAs. A lentiviral construct was used to overexpress the level of miR-142-3p in moDCs of NC. We examined the cytokines and chemokines in the supernatants of moDCs overexpressing miR-142-3p and used Transwell test, flow cytometric analysis and cell proliferation to observe the impact on CD4 T cells in moDC-CD4 T cell co-culture. moDCs in patients with SLE secreted increased level of IL-6, CCL2 and CCL5, with attraction of more CD4 T cells compared with NC. We found 18 differentially expressed microRNAs in moDCs of SLE patients by microarray, and target gene prediction showed some target genes of differentially expressed miRNAs were involved in cytokine regulation. miR-142-3p was verified among the highly expressed miRNAs in the SLE group and overexpressing miR-142-3p in moDCs of the NC group caused an increase of SLE-related cytokines, such as CCL2, CCL5, CXCL8, IL-6 and TNF-α. Moreover, moDCs overexpressed with miR-142-3p resulted in attraction of an increased number of CD4 T cells and in suppression of the proportion of Tregs in DC-CD4 T cell co-culture whereas the proliferation of CD4 T cells was not altered. The results demonstrated a role for miR-142-3p in regulating the pro-inflammatory function of moDCs in the pathogenesis of SLE. These findings suggested that miR-142-3p could serve as a novel therapeutic target for the treatment of SLE.