Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma - 24/12/11
, Andrew E. Williams, PhD b, , Sterghios A. Moschos, PhD c, Ketan Patel, PhD c, Christos Rossios, PhD b, Xiaoying Jiang, PhD a, Oona-Delpuech Adams, PhD c, Patricia Macedo, MD b, Richard Booton, PhD a, David Gibeon, MD b, Kian Fan Chung, PhD b, Mark A. Lindsay, PhD a, b, d, ⁎ 
Corresponding author: Mark A. Lindsay, PhD, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY United Kingdom.Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Severe asthma, CD8+ T cells, transcriptome, long noncoding RNA, microRNA
Abbreviations used : FDR, LCN, lncRNA, miRNA, qRT-PCR, Treg
Plan
| Supported by a National Institute for Health Research (NIHR) Translational Research Facility Grant (to E.T. and R.B.), Asthma UK (07/015 to A.E.W.), the Wellcome Trust (076111 to M.A.L. and 085935 to K.F.C.), the NIHR Royal Brompton Respiratory Biomedical Research Unit (to K.F.C.), and a Chinese Overseas Study Scholarship (to X.J.). |
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| Disclosure of potential conflict of interest: S. A. Moschos has received travel grants from Miltenyi Biotech and Caliper Life Sciences. K. F. Chung is a consultant for Gilead, is on the advisory board for Merck and GlaxoSmithKline, and has received research support from the Medical Research Council UK, Asthma UK, and the Wellcome Trust. The rest of the authors have declared that they have no conflict of interest. |
Vol 129 - N° 1
P. 95-103 - janvier 2012 Retour au numéro
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