期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 129, 期 1, 页码 95-103出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2011.08.011
关键词
Severe asthma; CD8(+) T cells; transcriptome; long noncoding RNA; microRNA
资金
- National Institute for Health Research (NIHR)
- Asthma UK [07/015]
- Wellcome Trust [076111, 085935]
- NIHR Royal Brompton Respiratory Biomedical Research Unit
- Chinese Overseas Study Scholarship
- Miltenyi Biotech and Caliper Life Sciences
- Medical Research Council UK
- Medical Research Council [G0801056B, G1000758, G1000758B] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10212] Funding Source: researchfish
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 IncRNA that might regulate CD8(+) T-cell function. (J Allergy Clin Immunol 2012; 129: 95-103.)
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