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Upregulation of miR‐155 in CD4 + T Cells Promoted Th1 Bias in Patients With Unstable Angina
Author(s) -
Chen Yanmei,
Li Lang,
Lu Yongguang,
Su Qiang,
Sun Yuhan,
Liu Yang,
Yang Dong
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24987
Subject(s) - downregulation and upregulation , gene knockdown , microrna , ectopic expression , unstable angina , microbiology and biotechnology , biology , cancer research , chemistry , immunology , medicine , cell culture , gene , genetics , myocardial infarction
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. J. Cell. Physiol. 230: 2498–2509, 2015. © 2015 Wiley Periodicals, Inc.