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Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a major clinical challenge mostly due to cigarette smoke (CS) exposure. Invariant natural killer T (iNKT) cells are potent immunoregulatory cells that have a crucial role in inflammation. In the current study, we investigate the role of iNKT cells in COPD pathogenesis. The frequency of activated NKT cells was found to be increased in peripheral blood of COPD patients relative to controls. In mice chronically exposed to CS, activated iNKT cells accumulated in the lungs and strongly contributed to the pathogenesis. The detrimental role of iNKT cells was confirmed in an acute model of oxidative stress, an effect that depended on interleukin (IL)-17. CS extracts directly activated mouse and human dendritic cells (DC) and airway epithelial cells (AECs) to trigger interferon? and/or IL-17 production by iNKT cells, an effect ablated by the anti-oxidant N-acetylcystein. In mice, this treatment abrogates iNKT-cell accumulation in the lung and abolished the development of COPD. Together, activation of iNKT cells by oxidative stress in DC and AECs participates in the development of experimental COPD, a finding that might be exploited at a therapeutic level.

SUBMITTER: Pichavant M

PROVIDER: S-EPMC3998637 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis.

Pichavant M M Rémy G G Bekaert S S Le Rouzic O O Kervoaze G G Vilain E E Just N N Tillie-Leblond I I Trottein F F Cataldo D D Gosset P P

Mucosal immunology 20131030 3

Chronic obstructive pulmonary disease (COPD) is a major clinical challenge mostly due to cigarette smoke (CS) exposure. Invariant natural killer T (iNKT) cells are potent immunoregulatory cells that have a crucial role in inflammation. In the current study, we investigate the role of iNKT cells in COPD pathogenesis. The frequency of activated NKT cells was found to be increased in peripheral blood of COPD patients relative to controls. In mice chronically exposed to CS, activated iNKT cells accu ...[more]

PMID: 24172846

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Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis.

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Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis.

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