title: Repeated Activation of Lung Invariant NKT Cells Results in Chronic Obstructive Pulmonary Disease-Like Symptoms.
abstract: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation, mucus hypersecretion, and emphysema, which lead to reduced lung function and breathlessness. The pathologies of COPD are due to an abnormal immune response. Invariant natural killer T (iNKT) cells are an important population of innate lymphocytes and have been implicated in the regulation of immune responses associated with a broad range of diseases including COPD. We have here analyzed the role of iNKT cells in a model of COPD induced by repeated intranasal administration of iNKT cell agonist α-galactosylceramide (α-GalCer). Our results demonstrated that mice that received repeated intranasal administration of α-GalCer had molecular and inflammatory features of COPD including airway inflammation with significant increases in infiltration of macrophages and lymphocytes, CD8+ T cells, as well as proinflammatory cytokines IL-6 and TNF-α. In particular, these mice also showed the presence of pulmonary emphysema, mucus production, and pulmonary fibrosis. Furthermore, neutralization of IL-4 reduced α-GalCer induced emphysema. This study indicates the importance of iNKT cells in the pathogenesis of COPD by an IL-4 dependent mechanism.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Cheng-Chiu
authors.initials: CC
authors.lastname: Tsao
authors.affiliation: Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan.|The Research Center of Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Po-Nien
authors.initials: PN
authors.lastname: Tsao
authors.affiliation: Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, WI, 53226, United States of America.|Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, 53226, United States of America.
authors.forename: Yi-Guang
authors.initials: YG
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chuang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis; D008168:Lung / Q000503:physiopathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D055611:Natural Killer T-Cells / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D005699:Galactosylceramides; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D053508:Matrix Metalloproteinase 12
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