TY - JOUR
T1 - Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma.
AU - Tsitsiou, Eleni
AU - Williams, Andrew Evan
AU - Moschos, Sterghios
AU - Patel, Ketan
AU - Rossios, Christos
AU - Jiang, Xiaoying
AU - Adams, Oona-Delpuech
AU - Macedo, Patricia
AU - Booton, Richard
AU - Gibeon, David
AU - Chung, Kian Fan
AU - Lindsay, Mark
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - Severe asthma
KW - transcriptome
KW - long noncoding RNA
KW - microRNA
U2 - 10.1016/j.jaci.2011.08.011
DO - 10.1016/j.jaci.2011.08.011
M3 - Article
VL - 129
SP - 95
EP - 103
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 1
ER -