title: Upregulation of miR-155 in CD4(+) T Cells Promoted Th1 Bias in Patients With Unstable Angina.
abstract: An imbalance between T helper 1 (Th1) and T helper 2 (Th2) cells has been reported to increase plaque instability in patients with unstable angina (UA). MicroRNAs play a vital role in the differentiation of CD4(+) T cells. However, the role of microRNAs in regulation of Th1/Th2 balance in UA remains unclear. In this study, we aimed to elucidate microRNA expression profiles of circulating CD4(+) T cells in UA and to explore the function of microRNAs in the Th1/Th2 balance. A total of 53 patients with UA and 31 control subjects without coronary artery disease were enrolled. Microarray analysis of the microRNA expression profiles of CD4(+) T cells revealed that miR-155 was the most significantly upregulated microRNA of the 451 differentially expressed microRNAs. The upregulation of miR-155 expression was positively correlated with the percentage of Th1 cells and interferon-gamma (IFN-γ) levels in patients with UA. In addition, overexpression of miR-155 in human circulating CD4(+) T cells promoted Th1 differentiation. Further studies identified IFN-γ receptor alpha chain (IFN-γ Rα) mRNA as a direct and functional target of miR-155. A luciferase reporter assay verified that miR-155 directly targeted IFN-γ Rα mRNA. Small-interfering RNA-mediated knockdown of IFN-γ Rα mRNA showed effects similar to those of ectopic miR-155 expression. Thus, our study indicated that upregulation of miR-155 in circulating CD4(+) T cells in patients with UA promoted a shift in the Th1/Th2 balance toward Th1 dominance by repressing IFN-γ Rα, which may subsequently enhance plaque instability.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
mesh_terms: D000789:Angina, Unstable / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology*; D018418:Th2 Cells / Q000166:cytology; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D035683:MicroRNAs; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C524942:MIRN155 microRNA, human