title: Dectin-2 promotes house dust mite-induced T helper type 2 and type 17 cell differentiation and allergic airway inflammation in mice.
abstract: The fact that sensitization against fungi is closely related to the severity of asthma suggests that immune systems recognizing fungi are involved in the pathogenesis of severe asthma. Recently, Dectin-2 (gene symbol, Clec4n), a C-type lectin receptor, has been shown to function as not only a major pattern-recognition receptor for fungi, but also a receptor for some components of house dust mite (HDM) extract, a major allergen for asthma. However, the roles of Dectin-2 in the induction of HDM-induced allergic airway inflammation remain largely unknown. Our objective was to determine the roles of Dectin-2 in HDM-induced allergic airway inflammation. We examined the roles of Dectin-2 in the induction of HDM-induced T helper (Th) 2 and Th17 cell differentiation and subsequent allergic airway inflammation by using Clec4n-deficient (Clec4n(-/-)) mice. We also investigated Dectin-2-expressing cells in the lung and their roles in HDM-induced allergic airway inflammation. Clec4n(-/-) mice showed significantly attenuated HDM-induced allergic airway inflammation and decreased Th2 and Th17 cell differentiation. Dectin-2 mRNA, together with Dectin-3 and Fc receptor-γ mRNAs, was expressed in CD11b(+) dendritic cells (DCs), but not in CD4(+) T cells or epithelial cells in the lung. CD11b(+) DCs isolated from Clec4n(-/-) mice expressed lower amounts of proinflammatory cytokines and costimulatory molecules, which could lead to Th2 and Th17 cell differentiation than those from wild-type mice. HDM-pulsed Clec4n(-/-) DCs were less efficient for the induction of allergic airway inflammation than HDM-pulsed wild-type DCs. In conclusion, Dectin-2 expressed on CD11b(+) DCs promotes HDM-induced Th2 and Th17 cell differentiation and allergic airway inflammation.
authors.affiliation: 1 Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Norimoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Arifumi
authors.initials: A
authors.lastname: Iwata
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tamachi
authors.forename: Masaya
authors.initials: M
authors.lastname: Yokota
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism*; D019476:Insect Proteins / Q000276:immunology*; D037181:Lectins, C-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D019476:Insect Proteins; D037181:Lectins, C-Type; D017452:Receptors, IgG; C445340:dectin-2, mouse
keywords: CD11b+ dendritic cells; Dectin-2; asthma; house dust mite