Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma.
J Allergy Clin Immunol
; 129(1): 95-103, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21917308
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Asma
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Activación de Linfocitos
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Linfocitos T CD8-positivos
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Perfilación de la Expresión Génica
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido