title: Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis.
abstract: Hypersensitivity pneumonitis (HP) is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP) is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL)-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif) ligand 5 (CXCL5) in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ishizuka
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masuo
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Suhara
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tateishi
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Makito
authors.initials: M
authors.lastname: Yasui
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Inase
mesh_terms: D000818:Animals; D001716:Bird Fancier's Lung / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D054365:Chemokine CXCL5 / Q000235:genetics / Q000276:immunology; D010856:Columbidae; D004195:Disease Models, Animal; D015769:Granuloma, Respiratory Tract / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology
chemical_list: D054365:Chemokine CXCL5; C094739:Cxcl5 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17