Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31(hi)Ly-6C(neg) bone marrow precursors in a mouse model of asthma.
Airway dendritic cells (DCs) are held responsible for inducing sensitization to inhaled antigen, leading to eosinophilic airway inflammation, typical of asthma. However, less information is available about the role of these cells in ongoing inflammation. In a mouse model of asthma, sensitization to ovalbumin (OVA) was induced by intratracheal injection of myeloid OVA-pulsed DCs. Upon OVA aerosol challenge and induction of eosinophilic airway inflammation in sensitized mice, there was a time-dependent and almost 100-fold increase in the number of MHCII(+) CD11b(+) CD11c(+) endogenous airway DCs as well as CD11b(+) blood DCs. The mechanism of this increase was studied. Adoptive transfer experiments demonstrated that accumulation of airway DCs was not due to reduced migration to the mediastinal lymph nodes. Rather, the massive increase in airway and lymph node DCs was supported by an almost 3-fold expansion of myeloid CD31(hi)Ly-6C(neg) hematopoietic precursor cells in the bone marrow (BM). There was no change in any of the other 5 populations revealed by CD31/Ly-6C staining. When these CD31(hi)Ly-6C(neg) BM precursors were sorted and grown in granulocyte macrophage-colony-stimulating factor, they differentiated into MHCII(+) CD11c(+) DCs. The same CD31(hi)Ly-6C(neg) precursors also expressed the eotaxin receptor CCR3 and differentiated into eosinophils when grown in interleukin 5. Serum levels of eotaxin were doubled in mice with inflammation. These findings in an animal model of asthma suggest that the BM increases its output of myeloid precursors to meet the enhanced demand for DCs and eosinophils in inflamed airways.
van Rijt
Leonie S
LS
Department of Pulmonary and Critical Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. vanrijt@longz.fgg.eur.nl
Prins
Jan-Bas
JB
Leenen
Pieter J M
PJ
Thielemans
Kris
K
de Vries
Victor C
VC
Hoogsteden
Henk C
HC
Lambrecht
Bart N
BN
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis
D000485:Allergens; D000950:Antigens, Ly; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010047:Ovalbumin