title: Persistent activation of dendritic cells after resolution of allergic airway inflammation breaks tolerance to inhaled allergens in mice.
abstract: BACKGROUND
  Polysensitization of patients who are allergic is a common feature. The underlying immunologic mechanism is not clear. The maturation status of dendritic cells (DCs) is considered to be important for priming naive T cells in the draining lymph nodes. We hypothesized that chronic airway inflammation can induce an enhanced maturation of airway DCs and facilitate subsequent priming to neoallergens.
  
  
  OBJECTIVE
  To investigate whether chronic airway inflammation could induce an altered activation of airway DCs in mice and whether this influences the development of allergic sensitization.
  
  
  METHODS
  Balb/c mice were repeatedly challenged with DCs to induce a chronic airway inflammation. We evaluated (1) the induction of the main characteristic features of human asthma including persistent remodeling, (2) the maturation status of airway DCs 1 month after inflammation resolved, (3) whether this influences tolerance to inhaled neoallergen, and (4) what type of T helper response would be induced by DCs.
  
  
  RESULTS
  Airway DCs displayed a mature phenotype after complete resolution of airway eosinophilia. Inhalation of a neoallergen without any adjuvant was able to induce airway inflammation in postinflammation lungs but not in control lungs. One month after inflammation, airway DCs were able to induce Th2 polarization in naive T cells consistent with the up-regulation of the Th2 skewing molecules Ym1/2 and OX-40L compared with DCs of control airways.
  
  
  CONCLUSIONS
  This study provides evidence that sustained maturation of DCs after resolution of Th2-mediated inflammation can contribute to polysensitization.
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Leonie S
authors.initials: LS
authors.lastname: van Rijt
authors.forename: Nanda
authors.initials: N
authors.lastname: Vos
authors.forename: Monique
authors.initials: M
authors.lastname: Willart
authors.forename: Femke
authors.initials: F
authors.lastname: Muskens
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Corine
authors.initials: C
authors.lastname: van der Horst
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
mesh_terms: D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012130:Respiratory Hypersensitivity
chemical_list: D000485:Allergens