Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma
Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma
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DOI：
10.1016/j.jaci.2011.08.011
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发表时间：
2012-01-01
影响因子：
14.2
通讯作者：
Lindsay, Mark A.
中科院分区：
文献类型：
--
作者：
Tsitsiou, Eleni;Williams, Andrew E.;Lindsay, Mark A.
背景：虽然以前的研究已经发现组织CD4(+) T细胞参与哮喘患者炎症反应的发展和维持，但对CD8(+) T细胞的作用知之甚少。现在越来越多的证据表明，microrna和其他非编码rna是t细胞功能的重要调节因子。目的：我们试图使用转录组学来确定非严重和严重哮喘患者循环CD4（+）和CD8(+) T细胞的激活状态。方法：采用微阵列、实时定量PCR或两种方法同时检测循环T细胞中mRNA和非编码RNA的表达。结果：mRNA表达比较显示重症哮喘患者外周血CD8(+) T细胞普遍改变，而CD4(+) T细胞无明显变化。与健康对照组相比，非严重哮喘患者的CD4（+）和CD8(+) T细胞未见变化。生物信息学分析表明，CD8(+) t细胞mRNA表达的变化与t细胞活化的多种途径相关。与mrna一样，我们也观察到严重哮喘患者CD8(+) T细胞中非编码RNA种类的表达发生了广泛的变化，包括天然反义、假基因、内含子长链非编码RNA （lncRNAs）和基因间lncRNAs。对microRNA表达谱的测量显示，CD8(+) T细胞中miR-28-5p的选择性下调，CD4（+）和CD8(+) T细胞中miR-146a和miR-146b的下调。结论：严重哮喘与循环CD8(+) T细胞活化有关，而与CD4(+) T细胞活化无关。这种反应与miR-146a/b和miR-28-5p的下调以及可能调节CD8(+) t细胞功能的多种IncRNA的表达变化有关。[J] .中华变态反应杂志，2012;29:95-103。
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.)