Abstract
BackgroundRecent 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.MethodsWe 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.ResultsmoDCs 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1158-z) contains supplementary material, which is available to authorized users.
Highlights
Recent studies have shown that alterations in the function of dendritic cells (DCs) are involved in the pathogenesis of systemic lupus erythematosus (SLE)
Pro-inflammatory function of monocyte-derived DCs (moDCs) in SLE Since cytokine production was one of the major functions of DCs with great biological importance, we first investigated whether the secreted concentration of some cytokines and chemokines in the supernatants of moDCs was different between SLE patients and healthy controls
We found that supernatants of moDCs in the SLE group attracted significantly more allogeneic CD4+ T cells than the control group and culture medium group though a Transwell assay (Fig. 1f)
Summary
Recent studies have shown that alterations in the function of dendritic cells (DCs) are involved in the pathogenesis of systemic lupus erythematosus (SLE). Systemic lupus erythematosus (SLE) is a complicated autoimmune disease impairing multiple organs. The disease predominantly affects women aged 15-40 years [1] with a female to male ratio of 9:1 [2]. Both genetic and environmental factors contribute to human SLE pathogenesis [3], but the etiology of SLE is not fully understood. Immunodysregulation in SLE involves the complex interplay of various immune cells and DCs are the master regulators for initiation, amplification, and perpetuation of the disease [5]. DCs could influence SLE in several ways including: presentation of self-antigens to autoreactive T cells; oversecretion of pro-inflammatory cytokines; and suppression of regulatory T cells and promotion of B cell autoantibody production, either directly
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