Accelerated airway dendritic cell maturation, trafficking, and elimination in a mouse model of asthma.
Pulmonary dendritic cells (DC) can induce both tolerogenic as well as inflammatory immune responses in the lung. Conversely, little is known about the impact of ongoing airway inflammation on pulmonary DC biology. In noninflammatory conditions, expression of T cell costimulatory molecules on mouse airway DCs is low and only upregulated after homing into draining thoracic lymph nodes. In this study, we reveal that ongoing allergic airway inflammation induces a premature upregulation of the T cell costimulatory molecules CD40, B7-2 and intercellular adhesion molecule 1 on DCs still present in the airways. In contrast, high surface expression of inducible costimulator ligand, involved in respiratory tolerance induction is restricted to DCs from noninflamed lungs. In addition, during inflammation the migratory flux of allergen-transporting airway DCs toward draining thoracic nodes increases both in amplitude as well as in speed. Remarkably, migratory DCs from inflamed airways are short-lived in the draining lymph nodes, a finding that is temporally associated with a marked loss of the antiapoptotic protein Bcl-2 in these cells. This study demonstrates the profound effects of ongoing allergen-driven airway inflammation on the dynamics of pulmonary DC physiology, a knowledge that could be exploited in the development of novel DC-based immunotherapies.
Vermaelen
Karim
K
Department of Respiratory Diseases, Ghent University Hospital, Belgium. Karim.Vermaelen@rug.ac.be
Pauwels
Romain
R
D000485:Allergens / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001249:Asthma / Q000276:immunology*; D051940:B7-2 Antigen; D018893:Bronchoalveolar Lavage; D039521:CD11c Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010047:Ovalbumin / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013909:Thorax / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D000485:Allergens; D015703:Antigens, CD; D051940:B7-2 Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin