title: IL-33 induces Th17-mediated airway inflammation via mast cells in ovalbumin-challenged mice.
abstract: Allergic asthma is characterized by infiltration of eosinophils, elevated Th2 cytokine levels, airway hyperresponsiveness, and IgE. In addition to eosinophils, mast cells, and basophils, a variety of cytokines are also involved in the development of allergic asthma. The pivotal role of eosinophils in the progression of the disease has been a subject of controversy. To determine the role of eosinophils in the progression of airway inflammation, we sensitized and challenged BALB/c wild-type (WT) mice and eosinophil-deficient ΔdblGATA mice with ovalbumin (OVA) and analyzed different aspects of inflammation. We observed increased eosinophil levels and a Th2-dominant response in OVA-challenged WT mice. In contrast, eosinophil-deficient ΔdblGATA mice displayed an increased proportion of mast cells and a Th17-biased response following OVA inhalation. Notably, the levels of IL-33, an important cytokine responsible for Th2 immune deviation, were not different between WT and eosinophil-deficient mice. We also demonstrated that mast cells induced Th17-differentiation via IL-33/ST2 stimulation in vitro. These results indicate that eosinophils are not essential for the development of allergic asthma and that mast cells can skew the immune reaction predominantly toward Th17 responses via IL-33 stimulation.
authors.affiliation: Department of Microbiology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Cho
authors.forename: Jee Won
authors.initials: JW
authors.lastname: Suh
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Sohn
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Park
authors.forename: Hyejin
authors.initials: H
authors.lastname: Lee
authors.forename: JiHee Lee
authors.initials: JL
authors.lastname: Kang
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Woo
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Cho
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002452:Cell Count; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin; D018123:Receptors, Interleukin / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D016085:Bronchoconstrictor Agents; D016207:Cytokines; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D016210:Methacholine Chloride; D010047:Ovalbumin