Liu Lu, Hua Mingqiang, Liu Chuanfang, He Na, Li Zhao, Ma Daoxin
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Oncotarget. 2016 Nov 22;7(47):76453-76463. doi: 10.18632/oncotarget.12949.
Both microRNAs and T helper (Th) cells involve in autoimmune diseases and their effects and interactions in immune thrombocytopenia (ITP) remain unclear. In the present study, we investigated the expression profiles of seven immune-related microRNAs (miR-155, 146a, 326, 142-3p, 17-5p, 21 and 181a) and the frequencies of four Th cells (Th1, Th2, Th17 and Treg) in peripheral blood mononuclear cell (PBMCs) of ITP patients and healthy controls. Platelet autoantibodies specific for GPIIb/IIIa or GPIb/IX were measured using MAIPA method. The regulating effect of miR-146a on Th differentiation was evaluated after using agomir. Our results showed that the expression of miR-146a, miR-326 or miR-142-3p in ITP patients was lower than that of controls. The frequencies of Treg cells were decreased, whereas the frequencies of Th17 and Th22 cells were increased significantly in ITP patients compared to those in controls. The expression levels of miR-142-3p and miR-146a were negatively correlated with Th17 cells,respectively. The expression of miR-146a was positively correlated with the frequencies of Treg cells and platelet counts.No significant correlation was found between the miRNAs expression and different autoantibody groups. The up-regulated miR-146a expression with agomir contributed to the differentiation of Th17 and Treg in ITP patients.Moreover, miR-146a was increased in the presence of DEX in PBMCs of ITP patients in vitro.Our study represents the abnormal expression profile of immune-related miRNAs in ITP patients, and miR-146a may be involved in Tregs differentiation and function.
微小RNA(miRNA)和辅助性T(Th)细胞均参与自身免疫性疾病,它们在免疫性血小板减少症(ITP)中的作用及相互作用仍不清楚。在本研究中,我们调查了ITP患者和健康对照外周血单个核细胞(PBMC)中7种免疫相关微小RNA(miR-155、146a、326、142-3p、17-5p、21和181a)的表达谱以及4种Th细胞(Th1、Th2、Th17和调节性T细胞(Treg))的频率。使用单克隆抗体特异性血小板抗原固定免疫吸附法(MAIPA)检测针对糖蛋白IIb/IIIa或糖蛋白Ib/IX的血小板自身抗体。使用激动剂(agomir)后评估miR-146a对Th分化的调节作用。我们的结果显示,ITP患者中miR-146a、miR-326或miR-142-3p的表达低于对照组。与对照组相比,ITP患者中Treg细胞的频率降低,而Th17和Th22细胞的频率显著增加。miR-142-3p和miR-146a 的表达水平分别与Th17细胞呈负相关。miR-146a的表达与Treg细胞频率和血小板计数呈正相关。微小RNA表达与不同自身抗体组之间未发现显著相关性。激动剂使miR-146a表达上调,有助于ITP患者中Th17和Treg的分化。此外,体外ITP患者PBMC中存在地塞米松(DEX)时miR-146a增加。我们的研究揭示了ITP患者中免疫相关微小RNA的异常表达谱,并且miR-146a可能参与Treg的分化和功能。