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J Allergy Clin Immunol. 2012 Jan;129(1):95-103. doi: 10.1016/j.jaci.2011.08.011. Epub 2011 Sep 13.

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

Author information

  • 1Respiratory Research Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom. m.a.lindsay@bath.ac.uk

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.

PMID:
21917308
DOI:
10.1016/j.jaci.2011.08.011
[PubMed - indexed for MEDLINE]
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