title: Distinct regulation of Th2 and Th17 responses to allergens by pulmonary antigen presenting cells in vivo.
abstract: Accumulating evidence demonstrates that both Th2 and Th17 responses are involved in the pathogenesis of allergic airway inflammation in animals as well as in humans. The lung contains diverse types of antigen presenting cells. However, the mechanism by which these antigen presenting cells regulate Th2 versus Th17 responses in the lung remains incompletely understood. Here, we show that intranasal administration of fungal protease allergen induced both Th2 and Th17 responses in the lung with different kinetics. Notably, depletion of CD11c(+) cells or macrophages greatly diminished the numbers of allergen-specific Th2 cells in the lung, the infiltration of eosinophils into the airway and airway hyperreactivity. In sharp contrast, depletion of the same antigen presenting cells significantly increased the numbers of allergen-specific Th17 cells in the lung and the infiltration of neutrophils into the airway. Moreover, although a subpopulation of lung epithelial cells express MHC II, lack of MHC II expression in parenchymal cells did not alter pulmonary Th2 and Th17 responses. Our results demonstrate that antigen presenting cells differentially regulate the generation of pulmonary Th2 and Th17 cells in response to intranasal protease allergens.
authors.affiliation: Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Hoyong
authors.initials: H
authors.lastname: Lim
authors.forename: Young Uk
authors.initials: YU
authors.lastname: Kim
authors.forename: Kyoungah
authors.initials: K
authors.lastname: Yun
authors.forename: Scott M
authors.initials: SM
authors.lastname: Drouin
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001230:Aspergillus / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005656:Fungal Proteins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010447:Peptide Hydrolases / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000485:Allergens; D039521:CD11c Antigen; D016207:Cytokines; D005656:Fungal Proteins; D000949:Histocompatibility Antigens Class II; D010447:Peptide Hydrolases
keywords: Allergen; CD11c(+) dendritic cell; Lung inflammation; Macrophage; Th17; Th2