title: United airways: circulating Th2 effector cells in an allergic rhinitis model are responsible for promoting lower airways inflammation.
abstract: BACKGROUND
  Allergic rhinitis (AR) and asthma often coexist and are referred to as 'united airways' disease. However, the molecular and cellular pathways that are crucially involved in the interaction between upper and lower airways remain to be identified.
  
  
  OBJECTIVE
  We sought to assess whether and how AR exacerbates lower airway inflammation upon allergen challenge in mice.
  
  
  METHODS
  We previously developed an intranasal ovalbumin (OVA)-driven AR model, characterized by nasal eosinophilic inflammation, enhanced serum levels of OVA-specific IgE and Th2 cytokine production in cervical lymph nodes. In OVA-sensitized mice with or without AR, a lower airway challenge was given, and after 24 h, lower airway inflammation was analysed.
  
  
  RESULTS
  We found that AR mice were more susceptible to eosinophilic inflammation following a lower airway OVA challenge than OVA-sensitized controls. AR mice manifested increased numbers of eosinophils in bronchoalveolar lavage fluid and increased inter-cellular adhesion molecule-1 (ICAM-1) expression on lung endothelium, when compared with OVA-sensitized controls. Depletion of T cells in OVA-challenged AR mice completely abrogated all hallmarks of lower airway inflammation, including enhanced IL-5 and tissue eosinophilia. Conversely, adoptive transfer of Th2 effector cells in naïve animals induced lower airway eosinophilic inflammation after challenge with OVA. Blocking T cell recirculation during AR development by the spingosine-1 analogue FTY720 also prevented lower airway inflammation including ICAM-1 expression in AR mice upon a single lower airway challenge.
  
  
  CONCLUSIONS
  Our mouse model of 'united airways' disease supports epidemiological and clinical data that AR has a significant impact on lower airway inflammation. Circulating Th2 effector cells are responsible for lung priming in AR mice, most likely through up-regulation of ICAM-1.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Rotterdam, The Netherlands. a.kleinjan@erasmusmc.nl
authors.forename: A
authors.initials: A
authors.lastname: KleinJan
authors.forename: M
authors.initials: M
authors.lastname: Willart
authors.forename: M
authors.initials: M
authors.lastname: van Nimwegen
authors.forename: K
authors.initials: K
authors.lastname: Leman
authors.forename: H C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: R W
authors.initials: RW
authors.lastname: Hendriks
authors.forename: B N
authors.initials: BN
authors.lastname: Lambrecht
mesh_terms: D000818:Animals; D001249:Asthma / Q000150:complications* / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D000068876:Fingolimod Hydrochloride; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects; D011409:Propylene Glycols / Q000627:therapeutic use; D012221:Rhinitis, Allergic, Perennial / Q000150:complications* / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D011409:Propylene Glycols; D010047:Ovalbumin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine