title: Dendritic cells and alveolar macrophages mediate IL-13-induced airway inflammation and chemokine production.
abstract: BACKGROUND
  IL-13 in the airway induces pathologies that are highly characteristic of asthma, including mucus metaplasia, airway hyperreactivity (AHR), and airway inflammation. As such, it is important to identify the IL-13-responding cell types that mediate each of the above pathologies. For example, IL-13's effects on epithelium contribute to mucus metaplasia and AHR. IL-13's effects on smooth muscle also contribute to AHR. However, it has been difficult to identify the cell types that mediate IL-13-induced airway inflammation.
  
  
  OBJECTIVE
  We sought to determine which cell types mediate IL-13-induced airway inflammation.
  
  
  METHODS
  We treated the airways of mice with IL-13 alone or in combination with IFN-γ. We associated the inhibitory effect of IFN-γ on IL-13-induced airway inflammation and chemokine production with cell types in the lung that coexpress IL-13 and IFN-γ receptors. We then evaluated IL-13-induced responses in CD11c promoter-directed diphtheria toxin receptor-expressing mice that were depleted of both dendritic cells and alveolar macrophages and in CD11b promoter-directed diphtheria toxin receptor-expressing mice that were depleted of dendritic cells.
  
  
  RESULTS
  Dendritic cell and alveolar macrophage depletion protected mice from IL-13-induced airway inflammation and CCL11, CCL24, CCL22, and CCL17 chemokine production. Preferential depletion of dendritic cells protected mice from IL-13-induced airway inflammation and CCL22 and CCL17 chemokine production but not from IL-13-induced CCL11 and CCL24 chemokine production. In either case mice were not protected from IL-13-induced AHR and mucus metaplasia.
  
  
  CONCLUSIONS
  Pulmonary dendritic cells and alveolar macrophages mediate IL-13-induced airway inflammation and chemokine production.
authors.affiliation: Department of Medicine, Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Crapster-Pregont
authors.forename: Janice
authors.initials: J
authors.lastname: Yeo
authors.forename: Raquel L
authors.initials: RL
authors.lastname: Sanchez
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kuperman
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D016130:Immunophenotyping; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism
chemical_list: D018925:Chemokines; D018793:Interleukin-13; D007371:Interferon-gamma