No defect in T-cell priming, secondary response, or tolerance induction in response to inhaled antigens in Fms-like tyrosine kinase 3 ligand-deficient mice.
BACKGROUND
Respiratory tract dendritic cells (DCs) are crucial for the regulation of immune responses to inhaled antigens. However, the precise function of the multiple DC subsets present in the lungs and the lung-draining lymph nodes is unknown. Fms-like tyrosine kinase 3 ligand (FLT3L) is a hematopoietic growth factor that drives the development of multiple subsets of DCs in the lymphoid organs.


OBJECTIVE
We sought to study the contribution of DC subsets in the regulation of the balance between tolerance and immunity against respiratory antigens by using FLT3L knockout mice.


METHODS
Phenotypic analysis of DC subsets in the airways and lungs of FLT3L knockout mice was performed. By using various experimental models, the role of FLT3L-dependent DCs in the priming of naive T cells, the presentation of inhaled antigen to previously primed T H 2 cells, and intranasal tolerance induction was addressed.


RESULTS
FLT3L knockout mice display a 90% reduction in lung parenchyma DCs but a normal number of airway DCs and blood monocytes. FLT3L knockout mice had a normal induction of eosinophilic inflammation in response to intranasal administration of allergen. FLT3L-dependent DCs were not required for the presentation of inhaled antigen to previously primed T H 2 cells, and normal induction of T-cell tolerance in response to inhaled antigen was observed in FLT3L knockout mice.


CONCLUSIONS
Airway DC development is independent of FLT3L. FLT3L-dependent DCs are not required for the development and maintenance of airway inflammation or for the induction of intranasal tolerance. Our results point to airway DCs as the major regulators of the balance between tolerance and immunity to inhaled antigens.
Walzer
Thierry
T
Amgen Inc., Seattle, WA 98119, USA.
Brawand
Pierre
P
Swart
David
D
Tocker
Joel
J
De Smedt
Thibaut
T
D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D017951:Antigen Presentation; D052179:Antigens, Plant; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000097:blood / Q000209:etiology / Q000276:immunology*; D007108:Immune Tolerance; D008168:Lung / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D012137:Respiratory System / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000172:deficiency* / Q000235:genetics
D000485:Allergens; D052179:Antigens, Plant; C060835:allergen CRa, cockroach; D040281:Vascular Endothelial Growth Factor Receptor-1