title: Peripheral blood dendritic cell subtypes are significantly elevated in subjects with asthma.
abstract: BACKGROUND
  Dendritic cells (DCs) are crucial for the processing of antigens, T lymphocyte priming and the development of asthma and allergy. Smokers with asthma display altered therapeutic behaviour and a reduction in endobronchial DC CD83 expression compared with non-smokers with asthma. No information is available on the impact of smoking on peripheral blood DC profiles.
  
  
  OBJECTIVE
  Determine peripheral blood DC profiles in subjects with and without asthma with differing smoking histories.
  
  
  METHODS
  Forty-three asthmatics (17 smokers, nine ex-smokers and 17 never-smokers) and 16 healthy volunteers (nine smokers and seven never-smokers) were recruited. Spirometry, exhaled nitric oxide and venesection was performed. DC elution was by flow cytometry via the expression of DC surface markers [plasmacytoid (pDC) (BDCA-2, CD303), type 1 conventional (cDC) (BDCA-1, CD1c), and type 2 cDC (BDCA-3, CD141)].
  
  
  RESULTS
  Subjects with asthma displayed increases in all DC subtypes compared with normal never-smokers: [type 1 cDCs - asthma [median% (IQR)]: 0.59% (0.41, 0.74), normal never-smokers: 0.35% (0.26, 0.43), P=0.013]; type 2 cDCs - asthma: 0.04% (0.02, 0.06), normal never-smokers: 0.02% (0.01, 0.03), P=0.008 and pDCs - asthma: 0.32% (0.27, 0.46), normal never-smokers: 0.22% (0.17, 0.31), P=0.043, and increased pDC and type 1 cDCs compared with normal smokers. Smoking did not affect DC proportions in asthma. Cigarette smoking reduced pDC proportions in normal subjects [normal never-smokers: 0.22% (0.17, 0.31); normal smokers: 0.09% (0.08, 0.15), P=0.003].
  
  
  CONCLUSIONS
  This study shows for the first time that subjects with asthma display a large increase in peripheral blood DC proportions. Cigarette smoking in asthma did not affect the peripheral blood DC profile but did suppress pDC proportions in non-asthmatic subjects. Asthma is associated with a significant increase in circulating DCs, reflecting increased endobronchial levels and the importance of DCs to the development and maintenance of asthma. (Clinical trials.gov identifier: NCT00411320)
authors.affiliation: Department of Respiratory Medicine, Institute of Infection, Immunity and Inflammation, Gartnavel General Hospital, University of Glasgow, Glasgow, UK. mark.spears@glasgow.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Spears
authors.forename: C
authors.initials: C
authors.lastname: McSharry
authors.forename: I
authors.initials: I
authors.lastname: Donnelly
authors.forename: L
authors.initials: L
authors.lastname: Jolly
authors.forename: M
authors.initials: M
authors.lastname: Brannigan
authors.forename: J
authors.initials: J
authors.lastname: Thomson
authors.forename: J
authors.initials: J
authors.lastname: Lafferty
authors.forename: R
authors.initials: R
authors.lastname: Chaudhuri
authors.forename: M
authors.initials: M
authors.lastname: Shepherd
authors.forename: E
authors.initials: E
authors.lastname: Cameron
authors.forename: N C
authors.initials: NC
authors.lastname: Thomson
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking