title: Th17/Treg ratio derived using DNA methylation analysis is associated with the late phase asthmatic response.
abstract: BACKGROUND
  The imbalance between Th17 and Treg cells has been studied in various diseases including allergic asthma but their roles have not been fully understood in the development of the late phase asthmatic response.
  
  
  OBJECTIVE
  To determine changes in Th17 and Treg cell numbers between isolated early responders (ERs) and dual responders (DRs) undergoing allergen inhalation challenge. To identify gene expression profiles associated with Th17 and Treg cells.
  
  
  METHODS
  14 participants (8 ERs and 6 DRs) with mild allergic asthma underwent allergen inhalation challenge. Peripheral blood was collected prior to and 2 hours post allergen challenge. DNA methylation analysis was used to quantifiy the relative frequencies of Th17, Tregs, total B cells, and total T cells. Gene expression from whole blood was measured using microarrays. Technical replication of selected genes was performed using nanoString nCounter Elements.
  
  
  RESULTS
  The Th17/Treg ratio significantly increased in DRs compared to ERs post allergen challenge compared to pre-challenge. Genes significantly correlated to Th17 and Treg cell counts were inversely correlated with each other. Genes significantly correlated with Th17/Treg ratio included the cluster of genes of the leukocyte receptor complex located on chromosome 19q 13.4.
  
  
  CONCLUSIONS
  Th17/Treg imbalance post-challenge may contribute to the development of the late phase inflammatory phenotype.
authors.affiliation: James Hogg Research Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.|Institute for HEART + LUNG Health, Vancouver, BC, Canada.|Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.
authors.forename: Amrit
authors.initials: A
authors.lastname: Singh
authors.affiliation: James Hogg Research Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.|Institute for HEART + LUNG Health, Vancouver, BC, Canada.|Vancouver Coastal Health Research Institute, Vancouver General Hospital, Vancouver, BC, Canada.|Department of Medicine, Division of Respiratory Medicine, UBC, Vancouver, BC, Canada.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: James Hogg Research Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.|Institute for HEART + LUNG Health, Vancouver, BC, Canada.|Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.
authors.forename: Jian
authors.initials: J
authors.lastname: Ruan
authors.affiliation: James Hogg Research Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.|Institute for HEART + LUNG Health, Vancouver, BC, Canada.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.affiliation: Epiontis GmbH, Berlin, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Olek
authors.affiliation: Epiontis GmbH, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hoffmueller
authors.affiliation: James Hogg Research Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.|Institute for HEART + LUNG Health, Vancouver, BC, Canada.|Vancouver Coastal Health Research Institute, Vancouver General Hospital, Vancouver, BC, Canada.|Department of Medicine, Division of Respiratory Medicine, UBC, Vancouver, BC, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Carlsten
authors.affiliation: Institute for HEART + LUNG Health, Vancouver, BC, Canada.|Vancouver Coastal Health Research Institute, Vancouver General Hospital, Vancouver, BC, Canada.|Department of Medicine, Division of Respiratory Medicine, UBC, Vancouver, BC, Canada.
authors.forename: J Mark
authors.initials: JM
authors.lastname: FitzGerald
authors.affiliation: Quebec Heart and Lung Institute, Laval University, Québec City, QC, Canada.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.affiliation: James Hogg Research Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.|Institute for HEART + LUNG Health, Vancouver, BC, Canada.|Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.|Department of Medicine, Division of Respiratory Medicine, UBC, Vancouver, BC, Canada.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Tebbutt
keywords: Allergen inhalation challenge; Asthma, Asthmatic response; DNA methylation; Epigenetic cell counting; Peripheral blood; Th17/Treg ratio, nCounter Elements