title: CD34 is required for dendritic cell trafficking and pathology in murine hypersensitivity pneumonitis.
abstract: BACKGROUND
  Although recent work has shown that CD34 plays an important role in the trafficking of inflammatory cells during Th2-biased inflammatory responses, its role in Th1/Th17-biased disease as well as dendritic cell (DC) trafficking is unknown.
  
  
  OBJECTIVE
  We used CD34-deficient mice (Cd34(-/-)) to investigate the role of CD34 in the Th1/Th17-biased lung inflammatory disease, hypersensitivity pneumonitis (HP).
  
  
  METHODS
  HP was induced in wild-type (wt) and Cd34(-/-) mice by repeated intranasal administration of Saccharopolyspora rectivirgula antigen. Lung inflammation was assessed by histology and analysis of bronchoalveolar lavage cells. Primary and secondary immune responses were evaluated by cytokine recall responses of pulmonary inflammatory cells as well as draining lymph node cells.
  
  
  RESULTS
  Cd34(-/-) mice were highly resistant to the development of HP and exhibited an inflammatory pattern more reflective of a primary response to S. rectivirgula rather than the chronic lymphocytosis that is typical of this disease. Cytokine recall responses from Cd34(-/-) lymph node cells were dampened and consistent with a failure of antigen-loaded Cd34(-/-) DCs to deliver antigen and prime T cells in the draining lymph nodes. In agreement with this interpretation, adoptive transfer of wt DCs into Cd34(-/-) mice was sufficient to restore normal sensitivity to HP. CD34 was found to be expressed by wt DCs, and Cd34(-/-) DCs exhibited an impaired ability to chemotax toward a subset of chemokines in vitro. Finally, expression of human CD34 in Cd34(-/-) mice restored normal susceptibility to HP.
  
  
  CONCLUSIONS
  We conclude that CD34 is expressed by mucosal DCs and plays an important role in their trafficking through the lung and to the lymph nodes. Our data also suggest that CD34 may play a selective role in the efficient migration of these cells to a subset of chemokines.
authors.affiliation: The Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada.
authors.forename: Marie-Renée
authors.initials: MR
authors.lastname: Blanchet
authors.forename: Jami L
authors.initials: JL
authors.lastname: Bennett
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gold
authors.forename: Elena
authors.initials: E
authors.lastname: Levantini
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
authors.forename: Melissa
authors.initials: M
authors.lastname: Girard
authors.forename: Yvon
authors.initials: Y
authors.lastname: Cormier
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
mesh_terms: D019264:Adoptive Transfer; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D018952:Antigens, CD34