Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma
Tsitsiou, E., Williams, A. E., Moschos, S. A., Patel, K., Rossios, C., Jiang, X., Adams, O. D., MacEdo, P., Booton, R., Gibeon, D., Chung, K. F. and Lindsay, M. 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.
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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.
|Creators||Tsitsiou, E., Williams, A. E., Moschos, S. A., Patel, K., Rossios, C., Jiang, X., Adams, O. D., MacEdo, P., Booton, R., Gibeon, D., Chung, K. F. and Lindsay, M. A.|
|Departments||Faculty of Science > Pharmacy & Pharmacology|
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