Upregulation of miR‐155 in CD4+ T Cells Promoted Th1 Bias in Patients With Unstable Angina

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.