title: Dectin-1 Plays an Important Role in House Dust Mite-Induced Allergic Airway Inflammation through the Activation of CD11b+ Dendritic Cells.
abstract: It is well known that sensitization against fungi is closely associated with severity of asthma. Dectin-1 (gene symbol Clec7a), a C-type lectin receptor, recognizes the fungal cell wall component β-glucan, as well as some component(s) in house dust mite (HDM) extract. However, the roles of Dectin-1 in HDM-induced allergic airway inflammation remain unclear. In this study, we used Dectin-1-deficient (Clec7a-/-) mice to examine whether Dectin-1 is involved in HDM-induced allergic airway inflammation. We found that HDM-induced eosinophil and neutrophil recruitment into the airways was significantly attenuated in Clec7a-/-mice compared with that in wild-type mice. In addition, HDM-induced IL-5, IL-13, and IL-17 production from mediastinum lymph node cells was reduced in HDM-sensitized Clec7a-/-mice. Dectin-1 was expressed on CD11b+dendritic cells (DCs), an essential DC subset for the development of allergic inflammation, but not on CD103+DCs, plasmacytoid DCs, or lung epithelial cells. Transcriptome analysis revealed that the expression of chemokine/chemokine receptors, including CCR7, which is indispensable for DC migration to draining lymph nodes, was decreased in Clec7a-/-DCs. In accordance with these results, the number of HDM-labeled CD11b+DCs in mediastinum lymph nodes was significantly reduced in Clec7a-/-mice compared with wild-type mice. Taken together, these results suggest that Dectin-1 expressed on CD11b+DCs senses some molecule(s) in HDM extract and plays a critical role in the induction of HDM-induced allergic airway inflammation by inducing the expression of chemokine/chemokine receptors in DCs.
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; hirose-kh@faculty.chiba-u.jp nakajimh@faculty.chiba-u.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Norimoto
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tamachi
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yokota
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Saku
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takatori
authors.affiliation: Department of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8670, Japan; and.
authors.forename: Shinobu
authors.identifier: 0000-0002-3802-8821
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; hirose-kh@faculty.chiba-u.jp nakajimh@faculty.chiba-u.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006967:Hypersensitivity / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D000099181:Dectin-1
chemical_list: D039741:Antigens, Dermatophagoides; D039481:CD11b Antigen; D037181:Lectins, C-Type; D000099181:Dectin-1