title: Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Respiratory Research Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom. m.a.lindsay@bath.ac.uk
authors.forename: Eleni
authors.initials: E
authors.lastname: Tsitsiou
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Williams
authors.forename: Sterghios A
authors.initials: SA
authors.lastname: Moschos
authors.forename: Ketan
authors.initials: K
authors.lastname: Patel
authors.forename: Christos
authors.initials: C
authors.lastname: Rossios
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Jiang
authors.forename: Oona-Delpuech
authors.initials: OD
authors.lastname: Adams
authors.forename: Patricia
authors.initials: P
authors.lastname: Macedo
authors.forename: Richard
authors.initials: R
authors.lastname: Booton
authors.forename: David
authors.initials: D
authors.lastname: Gibeon
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lindsay
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D022661:RNA, Untranslated