Langerin+ dendritic cells are responsible for LPS-induced reactivation of allergen-specific Th2 responses in postasthmatic mice.
Allergic asthma is a T cell-dependent inflammatory lung disease that results from complex interactions between genetic predisposition and environmental factors, including exposure to lipopolysaccharide (LPS). In this study, we have shown that airway LPS exposure was sufficient to induce airway hyperreactivity (AHR) and eosinophil recruitment in mice that had previously experienced an acute episode of allergic asthma. LPS-induced disease reactivation depended on the activation of allergen-specific CD4(+) T cells by a subset of lung langerin(+) dendritic cells (DCs) that retained the allergen. Upon LPS exposure, migration of langerin(+) DCs from lungs to draining lymph nodes increased and LPS-exposed langerin(+) DCs instructed CD4(+) T cells toward a T helper (Th) 2 response. Selective depletion of langerin(+) DCs prevented LPS-induced eosinophil recruitment and T-cell activation, further demonstrating a critical role for langerin(+) DCs in disease reactivation. This finding provides a possible explanation for the subclinical worsening of asthmatics following exposure to low-dose LPS.
Université de Nice-Sophia Antipolis, Valbonne, France.
A
A
Ortiz-Stern
A
A
Kanda
C
C
Mionnet
J
J
Cazareth
A
A
Lazzari
S
S
Fleury
D
D
Dombrowicz
N
N
Glaichenhaus
V
V
Julia
D000485:Allergens / Q000276:immunology; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D001249:Asthma / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008213:Lymphocyte Activation; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000485:Allergens; D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D037241:Mannose-Binding Lectins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin