Transcriptome analysis shows activation of circulating CD8 + T cells in patients with severe asthma

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 1; pp. 95 - 103
• Main Authors: Tsitsiou, Eleni, Williams, Andrew E., Moschos, Sterghios A., Patel, Ketan, Rossios, Christos, Jiang, Xiaoying, Adams, Oona-Delpuech, Macedo, Patricia, Booton, Richard, Gibeon, David, Chung, Kian Fan, Lindsay, Mark A.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.01.2012; Elsevier; Elsevier Limited
• Subjects: Adult; Airway management; Allergy and Immunology; Asthma; Asthma - genetics; Asthma - immunology; bioinformatics; Biological and medical sciences; CD4-positive T-lymphocytes; CD4-Positive T-Lymphocytes - immunology; CD8 + T cells; CD8-positive T-lymphocytes; CD8-Positive T-Lymphocytes - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Humans; Immunopathology; inflammation; long noncoding RNA; Lymphocyte Activation - genetics; Lymphocytes; Male; Medical sciences; messenger RNA; microarray technology; microRNA; MicroRNAs; MicroRNAs - metabolism; Middle Aged; non-coding RNA; patients; Proteins; pseudogenes; quantitative polymerase chain reaction; RNA, Messenger - metabolism; RNA, Untranslated - metabolism; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severe asthma; Signal Transduction; Software; Studies; transcriptome; transcriptomics; Values; Young Adult; lncRNA; FDR; transcriptome; LCN; qRT-PCR; Treg; long noncoding RNA; microRNA; miRNA; CD8 + T cells; Severe asthma; Lipocalin 2; Quantitative RT-PCR; False discovery rate; Regulatory T; Human; Immunopathology; RNA interference; RNA; Micro RNA; Non coding sequence; Transcriptome; Activation; T cells; Gene silencing; Immunology; CD8; CD8 T lymphocyte
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2011.08.011

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. We sought to use transcriptomics to determine the activation state of circulating CD4 + and CD8 + T cells in patients with nonsevere and severe asthma. mRNA and noncoding RNA expression in circulating T cells was measured by means of microarray, quantitative real-time PCR, or both. 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. 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.