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

• DOI: 10.1038/mi.2013.75
• Publication Date: 2013-10-30T13:18:29Z
• Authors: M Pichavant; G Rémy; S Bekaert; O Le Rouzic; G Kervoaze; E Vilain; N Just; I Tillie-Leblond; F Trottein; D Cataldo; P Gosset
• Keywords: Mice, Knockout; 0303 health sciences; Antigen-Presenting Cells; Dendritic Cells; Lymphocyte Activation; Article; Antioxidants; 3. Good health; Disease Models, Animal; Mice; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; 03 medical and health sciences; Benzene Derivatives; Animals; Humans; Natural Killer T-Cells; Tobacco Smoke Pollution; Lymphocyte Count; Lung

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 interferonγ 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.