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

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• 作者：Eleni Tsitsiou ; PhD^a ; ^&lowast ; ; Andrew E. Williams ; PhD^b ; ^&lowast ; ; 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 ; ^{m.a.lindsay@bath.ac.uk}
• 关键词：Severe asthma ; CD8+ T cells ; transcriptome ; long noncoding RNA ; microRNA
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：January, 2012
• 年：2012
• 卷：129
• 期：1
• 页码：95-103
• 全文大小：139 K

文摘

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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.