Repeated Activation of Lung Invariant NKT Cells Results in Chronic Obstructive Pulmonary Disease-Like Symptoms. PLoS One 2016;11(1):e0147710
Date
01/27/2016Pubmed ID
26811900Pubmed Central ID
PMC4727802DOI
10.1371/journal.pone.0147710Scopus ID
2-s2.0-84958567904 12 CitationsAbstract
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 I?-galactosylceramide (I?-GalCer). Our results demonstrated that mice that received repeated intranasal administration of I?-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-I?. In particular, these mice also showed the presence of pulmonary emphysema, mucus production, and pulmonary fibrosis. Furthermore, neutralization of IL-4 reduced I?-GalCer induced emphysema. This study indicates the importance of iNKT cells in the pathogenesis of COPD by an IL-4 dependent mechanism.
Author List
Tsao CC, Tsao PN, Chen YG, Chuang YHAuthor
Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Administration, IntranasalAnimals
Bronchoalveolar Lavage Fluid
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Galactosylceramides
Inflammation
Interleukin-4
Interleukin-6
Lung
Lymphocyte Activation
Macrophages
Matrix Metalloproteinase 12
Mice
Mice, Inbred BALB C
Natural Killer T-Cells
Pulmonary Disease, Chronic Obstructive
Tumor Necrosis Factor-alpha
