Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma.
Dendritic cells (DCs) appear to be strategically implicated in allergic diseases, including asthma. Matrix metalloproteinase (MMP)-9 mediates transmigration of inflammatory leukocytes across basement membranes. This study investigated the role of MMP-9 in airway DC trafficking during allergen-induced airway inflammation. MMP-9 gene deletion affected the trafficking of pulmonary DCs in a specific way: only the inflammatory transmigration of DCs into the airway lumen was impaired, whereas DC-mediated transport of airway Ag to the thoracic lymph nodes remained unaffected. In parallel, the local production of the Th2-attracting chemokine CC chemokine ligand 17/thymus and activation-regulated chemokine, which was highly concentrated in purified lung DCs, fell short in the airways of allergen-exposed MMP-9(-/-) mice. This was accompanied by markedly reduced peribronchial eosinophilic infiltrates and impaired allergen-specific IgE production. We conclude that the specific absence of MMP-9 activity inhibits the development of allergic airway inflammation by impairing the recruitment of DCs into the airways and the local production of DC-derived proallergic chemokines.
Vermaelen
Karim Y
KY
Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium. Karim.Vermaelen@rug.ac.be
Cataldo
Didier
D
Tournoy
Kurt
K
Maes
Tania
T
Dhulst
An
A
Louis
Renaud
R
Foidart
Jean-Michel
JM
Noël
Agnès
A
Pauwels
Romain
R
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000096:biosynthesis; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008482:Mediastinum; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D020545:Respiratory Mucosa / Q000201:enzymology / Q000276:immunology / Q000473:pathology
D000485:Allergens; C499538:Ccl17 protein, mouse; C515483:Ccl22 protein, mouse; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D010047:Ovalbumin; D020780:Matrix Metalloproteinase 9