Elevated expression of miR-142-3p is related to the pro-inflammatory function of monocyte-derived dendritic cells in SLE.
Elevated expression of miR-142-3p is related to the pro-inflammatory function of monocyte-derived dendritic cells in SLE.
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miR-142-3p 表达升高与 SLE 中单核细胞来源的树突状细胞的促炎功能相关
DOI：
10.1186/s13075-016-1158-z
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发表时间：
2016-11-16
影响因子：
4.9
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Wang Y;Liang J;Qin H;Ge Y;Du J;Lin J;Zhu X;Wang J;Xu J
研究背景近年来的研究表明，树突状细胞（DCs）功能的改变参与了系统性红斑狼疮（SLE）的发病机制。然而，这种改变的机制尚不清楚。方法我们在体外培养单核细胞来源的DC（moDC），并检测了阴性对照（NC）和活动期SLE患者的moDC上清液中的细胞因子和趋化因子。然后，我们分析了SLE患者中LPS刺激的moDCs的microRNA（miRNAs），并使用实时PCR来验证差异表达的miRNAs。使用慢病毒构建体来过表达NC的moDC中miR-142- 3 p的水平。结果SLE患者的moDC分泌IL-6、CCL 2和CCL 5的水平明显高于正常对照组（P < 0. 05），且对CD 4 + T细胞的吸引能力明显高于正常对照组（P < 0. 05）。通过基因芯片技术在SLE患者moDCs中发现了18个差异表达的microRNA，靶基因预测显示部分差异表达的microRNA的靶基因参与了细胞因子的调控。miR-142- 3 p在SLE组高表达的miRNAs中得到证实，并且在NC组的moDCs中过表达miR-142- 3 p引起SLE相关细胞因子如CCL 2、CCL 5、CXCL 8、IL-6和TNF-α的增加。此外，与miR-142- 3 p过表达的moDCs导致在DC-CD 4 +T细胞共培养的CD 4 +T细胞的数量增加的吸引力和抑制的比例，而CD 4 +T细胞的增殖是不改变的。这些发现表明miR-142- 3 p可以作为治疗SLE的新靶点。
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.
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影响因子：
4.9
作者：
Fransen JH;van der Vlag J;Ruben J;Adema GJ;Berden JH;Hilbrands LB
通讯作者：
Hilbrands LB
影响因子：
2.6
作者：
Dai, Y.;Huang, Y-S;Yin, Y-B
通讯作者：
Yin, Y-B
影响因子：
4
作者：
Henriques, Ana;Ines, Luis;Paiva, Artur
通讯作者：
Paiva, Artur
影响因子：
20.3
作者：
Dunand-Sauthier, Isabelle;Santiago-Raber, Marie-Laure;Reith, Walter
通讯作者：
Reith, Walter
影响因子：
2.6
作者：
Kawasaki, M.;Fujishiro, M.;Sekigawa, I.
通讯作者：
Sekigawa, I.