Fcgamma receptor-mediated antigen uptake by lung DC contributes to allergic airway hyper-responsiveness and inflammation.
During asthma, lung DC capture and process antigens to initiate and maintain allergic Th2 cell responses to inhaled allergens. The aim of the study was to investigate whether allergen-specific IgG, generated during sensitization, can potentiate the acute airway inflammation through Fcgamma receptor (FcgammaR)-mediated antigen uptake and enhance antigen presentation resulting in augmented T-cell proliferation. We examined the impact of antigen presentation and T-cell stimulation on allergic airway hyperresponsiveness and inflammation using transgenic and gene-deficient mice. Both airway inflammation and eosinophilia in bronchoalveolar lavage fluid were markedly reduced in sensitized and challenged FcgammaR-deficient mice. Lung DC of WT, but not FcgammaR-deficient mice, induced increased antigen-specific CD4+ T-cell proliferation when pulsed with anti-OVA IgG immune complexes. Intranasal application of anti-OVA IgG immune complexes resulted in enhanced airway inflammation, eosinophilia and Th2 cytokine release, mediated through enhanced antigen-specific T-cell proliferation in vivo. Finally, antigen-specific IgG in the serum of sensitized mice led to a significant increase of antigen-specific CD4+ T-cell proliferation induced by WT, but not FcgammaR-deficient, lung DC. We conclude that FcgammaR-mediated enhanced antigen presentation and T-cell stimulation by lung DC has a significant impact on inflammatory responses following allergen challenge in asthma.
Institute for Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Christina
C
Hartwig
Miriam
M
Mazzega
Hannelore
H
Constabel
Jayendra K
JK
Krishnaswamy
J Engelbert
JE
Gessner
Armin
A
Braun
Thomas
T
Tschernig
Georg M N
GM
Behrens
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D001249:Asthma / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology*; D007249:Inflammation; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics
C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D008222:Lymphokines; C111390:OVA 323-339; D010446:Peptide Fragments; D017452:Receptors, IgG; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D010047:Ovalbumin