title: A role for dendritic cells in bleomycin-induced pulmonary fibrosis in mice?
abstract: BACKGROUND
  Lung dendritic cells (DCs) have been shown to accumulate in human fibrotic lung disease, but little is known concerning a role for DCs in the pathogenesis of fibrotic lung.
  
  
  OBJECTIVE
  To characterize lung DCs in an in vivo model of bleomycin-induced pulmonary fibrosis in mice.
  
  
  METHODS
  We characterized the kinetics and activation of pulmonary DCs during the course of bleomycin-induced lung injury by flow cytometry on lung single-cell suspensions. We also characterized the lymphocytes accumulating in bleomycin lung and the chemokines susceptible to favor the recruitment of immune cells.
  
  
  RESULTS
  We show, for the first time, that increased numbers of CD11c(+)/major histocompatibility complex class II(+) DCs, including CD11b(hi) monocyte-derived inflammatory DCs, infiltrate the lung of treated animals during the fibrotic phase of the response to bleomycin. These DCs are mature DCs expressing CD40, CD86, and CD83. They are associated with increased numbers of recently activated memory T cells expressing CD44, CD40L, and CD28, suggesting that fully mature DCs and Ag-experienced T cells can drive an efficient effector immune response within bleomycin lung. Most importantly, when DCs are inactivated with VAG539, a recently described new immunomodulator, VAG539 treatment attenuates the hallmarks of bleomycin lung injury.
  
  
  CONCLUSIONS
  These findings identify lung DCs as key proinflammatory cells potentially able to sustain pulmonary inflammation and fibrosis in the bleomycin model.
authors.affiliation: INSERM U700, Université Paris Diderot-Paris 7, UFR de Médecine-site Bichat, France.
authors.forename: Claudie
authors.initials: C
authors.lastname: Bantsimba-Malanda
authors.forename: Joëlle
authors.initials: J
authors.lastname: Marchal-Sommé
authors.forename: Delphine
authors.initials: D
authors.lastname: Goven
authors.forename: Olivia
authors.initials: O
authors.lastname: Freynet
authors.forename: Laurence
authors.initials: L
authors.lastname: Michel
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
authors.forename: Paul
authors.initials: P
authors.lastname: Soler
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007155:Immunologic Factors / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008285:Major Histocompatibility Complex / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D007155:Immunologic Factors; D001761:Bleomycin