title: Monocyte-derived dendritic cell recruitment and allergic T(H)2 responses after exposure to diesel particles are CCR2 dependent.
abstract: BACKGROUND
  The inhalation of diesel exhaust particles (DEPs) is associated with increased sensitization toward inhaled allergens. Dendritic cells (DCs) are important mediators in immune regulation. We previously showed that the inhalation of DEPs increased the accumulation of DCs in the lung and enhanced the T(H)2 response in the mediastinal lymph node.
  
  
  OBJECTIVE
  We hypothesized that CC chemokine receptors CCR2, CCR5, and CCR6 critically mediate the DC recruitment upon exposure to DEPs and that these CC chemokine receptors are important in the DEP-induced T(H)2 response.
  
  
  METHODS
  We exposed CCR2 knockout, CCR5 knockout, CCR6 knockout, and wild-type mice to DEPs and examined the pulmonary monocyte and DC accumulation. By an adoptive transfer experiment, we assessed the direct involvement of CCR2 and CCR6 in the recruitment of blood monocytes toward the lung upon exposure to DEPs. We also examined the T(H)2 cytokine production in the mediastinal lymph nodes of DEP-exposed CCR2 knockout and CCR6 knockout mice.
  
  
  RESULTS
  We observed that the DEP-induced monocyte and monocyte-derived DC recruitment was completely abolished in CCR2 knockout mice. CCR6 knockout mice also showed impaired monocyte recruitment upon exposure to DEPs. In contrast, monocyte and DC recruitment was comparable between DEP-exposed wild-type and CCR5 knockout mice. The impaired monocyte-derived DC recruitment in DEP-exposed CCR2 knockout, not CCR6 knockout, mice resulted in an abolished T(H)2 response in the mediastinal lymph node.
  
  
  CONCLUSIONS
  These data suggest that monocyte-derived DCs, recruited in a CCR2-dependent manner, are critical in inducing T(H)2 responses upon inhalation of DEPs.
authors: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. sharen.provoost@UGent.be
authors: Sharen
authors: S
authors: Provoost
authors: Tania
authors: T
authors: Maes
authors: Guy F
authors: GF
authors: Joos
authors: Kurt G
authors: KG
authors: Tournoy
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D018893:Bronchoalveolar Lavage; D018925:Chemokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D054399:Receptors, CCR6 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; C498126:CCR6 protein, mouse; C515335:Ccr2 protein, mouse; D018925:Chemokines; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D054399:Receptors, CCR6; D001335:Vehicle Emissions