LAPCs contribute to the pathogenesis of allergen-induced allergic airway inflammation in mice.
BACKGROUND
The inflammatory immune response associated with allergic airway inflammation in asthma involves T helper type 2 (Th2) immunity. Given the data that a newly described late activator antigen-presenting cell (LAPC) population promotes Th2 immunity in viral infections, we undertook studies to investigate whether LAPCs have a pathogenic role in allergic airway inflammation.


METHODS
We employed acute ovalbumin (OVA) and house dust mite (HDM) sensitization and challenge models to establish allergic airway inflammation in mice, followed by the analysis of lungs and draining lymph node (DLN) cell infiltrates, immunoglobulin E (IgE) production, and airway hyper-responsiveness (AHR). We tested whether adoptive transfer of LAPCs isolated from mice with established allergic airway inflammation augments the development of sensitization in naïve mice.


RESULTS
We provide evidence that in both OVA and HDM mouse models of allergic inflammation, LAPCs accumulate in the lungs and draining lymph nodes (DLNs), concomitant with the onset of lung pathology, allergen-specific IgE production, eosinophilia, and Th2 cytokine production. Adoptive transfer experiments using OVA-activated LAPCs reveal exacerbation of disease pathology with an increase in lung inflammatory cells, eosinophilia, circulating IgE, Th2 cytokine production, and a worsening of AHR. OVA-activated LAPCs preferentially increased GATA-3 induction in naïve CD4(+) T cells.


CONCLUSIONS
Together, these data suggest an important role for LAPCs in polarizing the Th2 response in mouse models of allergic airway inflammation.
Toronto General Research Institute, University Health Network, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
C
C
Hawkshaw
J A
JA
Scott
C-W
CW
Chow
E N
EN
Fish
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D007073:Immunoglobulin E; D010047:Ovalbumin
Th2 immune response; allergic airway inflammation; late activator antigen-presenting cell