title: A critical role of Dectin-1 in hypersensitivity pneumonitis.
abstract: OBJECTIVE
  Hypersensitivity pneumonitis (HP) is a pulmonary disease caused by repeated exposure to various aspiration antigens, including bacteria and fungi. Although TLRs are known to be required for the generation of HP triggered by bacteria, the significance of fungal receptors remains unclear. The present study aimed to investigate whether Dectin-1 and Dectin-2 contribute to the development of experimental HP triggered by the fungus Trichosporon asahii (T. asahii) that causes summer-type HP.
  
  
  METHODS
  We investigated the binding between Dectin-Fc protein and T. asahii by a dot blot assay. We performed the histological and flow cytometric analysis in the HP model using Dectin-1-deficient (Dectin-1(-/-)) and Dectin-2(-/-) mice. We also investigated Th17/Th1 responses in lung cells, and measured an IL-17-promoting cytokine IL-23 from bone marrow-derived dendritic cells (BMDCs) by ELISA.
  
  
  RESULTS
  Dectin-1 bound more strongly to T. asahii than Dectin-2. Dectin-1(-/-) mice barely developed HP, whereas both wild-type mice and Dectin-2(-/-) mice developed similar lung diseases. Dectin-1 deficiency decreased the infiltration of neutrophils and monocyte-derived macrophages and repressed the expansion of lung CD4(+)IL-17A(+) cells. The production of IL-23 p19 was reduced in Dectin-1(-/-) BMDCs.
  
  
  CONCLUSIONS
  These data suggested Dectin-1 plays a critical role in the development of fungus-induced HP.
authors.affiliation: Department of Respiratory Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.|Department of Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa Prefecture, 920-0293, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Higashino-Kameda
authors.affiliation: Department of Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa Prefecture, 920-0293, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yabe-Wada
authors.affiliation: Department of Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa Prefecture, 920-0293, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Matsuba
authors.affiliation: Department of Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa Prefecture, 920-0293, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Anzawa
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mochizuki
authors.affiliation: Laboratory of Space and Environmental Medicine, Teikyo University, Hachioji, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Makimura
authors.affiliation: Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Center for Animal Disease Models, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Respiratory Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Toga
authors.affiliation: Department of Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa Prefecture, 920-0293, Japan. aki-n@kanazawa-med.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D053759:Interleukin-23 / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058504:Th17 Cells / Q000276:immunology; D014250:Trichosporon; D000099181:Dectin-1
chemical_list: D053759:Interleukin-23; D037181:Lectins, C-Type; D000099181:Dectin-1; C445340:dectin-2, mouse
keywords: Dectin-1; Hypersensitivity pneumonitis; Th17; Trichosporon asahii