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Repeated Activation of Lung Invariant NKT Cells Results in Chronic Obstructive Pulmonary Disease-Like Symptoms. PLoS One 2016;11(1):e0147710

Date

01/27/2016

Pubmed ID

26811900

Pubmed Central ID

PMC4727802

DOI

10.1371/journal.pone.0147710

Scopus ID

2-s2.0-84958567904   12 Citations

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 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 YH

Author

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Intranasal
Animals
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