Tsitsiou, E;
Jiang, X;
Booton, R;
Lindsay, MA;
Williams, AE;
Rossios, C;
MacEdo, P;
... Adams, O-D; + view all
(2012)
Transcriptome analysis shows activation of circulating CD8 T cells in patients with severe asthma.
Journal of Allergy and Clinical Immunology
, 129
(1)
95 - 103.
10.1016/j.jaci.2011.08.011.
Preview |
Text
Final Text 2.pdf Download (340kB) | Preview |
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. © 2011 American Academy of Allergy, Asthma & Immunology.
Archive Staff Only
 |
View Item |
