title: Genome-Wide Methylation Study Identifies an IL-13-induced Epigenetic Signature in Asthmatic Airways.
abstract: BACKGROUND
  Epigenetic changes to airway cells have been proposed as important modulators of the effects of environmental exposures on airway diseases, yet no study to date has shown epigenetic responses to exposures in the airway that correlate with disease state. The type 2 cytokine IL-13 is a key mediator of allergic airway diseases, such as asthma, and is up-regulated in response to many asthma-promoting exposures.
  
  
  OBJECTIVE
  To directly study the epigenetic response of airway epithelial cells (AECs) to IL-13 and test whether IL-13-induced epigenetic changes differ between individuals with and without asthma.
  
  
  METHODS
  Genome-wide DNA methylation and gene expression patterns were studied in 58 IL-13-treated and untreated primary AEC cultures and validated in freshly isolated cells of subjects with and without asthma using the Illumina Human Methylation 450K and HumanHT-12 BeadChips. IL-13-mediated comethylation modules were identified and correlated with clinical phenotypes using weighted gene coexpression network analysis.
  
  
  RESULTS
  IL-13 altered global DNA methylation patterns in cultured AECs and were significantly enriched near genes associated with asthma. Importantly, a significant proportion of this IL-13 epigenetic signature was validated in freshly isolated AECs from subjects with asthma and clustered into two distinct modules, with module 1 correlated with asthma severity and lung function and module 2 with eosinophilia.
  
  
  CONCLUSIONS
  These results suggest that a single exposure of IL-13 may selectively induce long-lasting DNA methylation changes in asthmatic airways that alter specific AEC pathways and contribute to asthma phenotypes.
authors.affiliation: 1 Department of Human Genetics.
authors.forename: Jessie
authors.initials: J
authors.lastname: Nicodemus-Johnson
authors.affiliation: 1 Department of Human Genetics.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Naughton
authors.affiliation: 2 Section of Pulmonary and Critical Care Medicine.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Sudi
authors.affiliation: 2 Section of Pulmonary and Critical Care Medicine.
authors.forename: Kyle
authors.initials: K
authors.lastname: Hogarth
authors.affiliation: 2 Section of Pulmonary and Critical Care Medicine.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Naurekas
authors.affiliation: 1 Department of Human Genetics.|3 Section of Genetic Medicine, Department of Medicine, and.|4 Department of Statistics, University of Chicago, Chicago, Illinois.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
authors.affiliation: 2 Section of Pulmonary and Critical Care Medicine.
authors.forename: Anne I
authors.initials: AI
authors.lastname: Sperling
authors.affiliation: 2 Section of Pulmonary and Critical Care Medicine.
authors.forename: Julian
authors.initials: J
authors.lastname: Solway
authors.affiliation: 2 Section of Pulmonary and Critical Care Medicine.
authors.forename: Steven R
authors.initials: SR
authors.lastname: White
authors.affiliation: 1 Department of Human Genetics.
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics*; D002478:Cells, Cultured; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D008297:Male
chemical_list: D018793:Interleukin-13
keywords: IL-13; airway epithelial cells; asthma; epigenetic signature