Tsitsiou, Eleni and Williams, Andrew E. and Moschos, Sterghios A. and Patel, Ketan and Rossios, Christos and Jiang, Xiaoying and Adams, Oona-Delpuech and Macedo, Patricia and Booton, Richard and Gibeon, David and Chung, Kian Fan and Lindsay, Mark A. (2012) Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma. Journal of Allergy and Clinical Immunology, 129 (1). pp. 95-103. ISSN 0091-6749
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Official URL: http://dx.doi.org/10.1016/j.jaci.2011.08.011
Background - Although previous studies have implicated tissue CD4+ T cells in the development and maintenance of the inflammatory response in asthmatic patients, little is known about the role of CD8+ T cells. There is now accumulating evidence that microRNAs and other noncoding RNAs are important regulators of T-cell function. Objectives - We sought to use transcriptomics to determine the activation state of circulating CD4+ and CD8+ T cells in patients with nonsevere and severe asthma. Methods - mRNA and noncoding RNA expression in circulating T cells was measured by means of microarray, quantitative real-time PCR, or both. Results - Comparison of mRNA expression showed widespread changes in the circulating CD8+ but not CD4+ T cells from patients with severe asthma. No changes were observed in the CD4+ and CD8+ T cells in patients with nonsevere asthma versus those in healthy control subjects. Bioinformatics analysis showed that the changes in CD8+ T-cell mRNA expression were associated with multiple pathways involved in T-cell activation. As with mRNAs, we also observed widespread changes in expression of noncoding RNA species, including natural antisense, pseudogenes, intronic long noncoding RNAs (lncRNAs), and intergenic lncRNAs in CD8+ T cells from patients with severe asthma. Measurement of the microRNA expression profile showed selective downregulation of miR-28-5p in CD8+ T cells and reduction of miR-146a and miR-146b in both CD4+ and CD8+ T cells. Conclusions - Severe asthma is associated with the activation of circulating CD8+ T cells but not CD4+ T cells. This response is correlated with the downregulation of miR-146a/b and miR-28-5p, as well as changes in the expression of multiple species of lncRNA that might regulate CD8+ T-cell function.
|Research Community:||University of Westminster > Life Sciences, School of|
|Deposited On:||15 Sep 2011 16:14|
|Last Modified:||07 Jun 2012 16:29|
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