krn-7000 and Pulmonary-Disease--Chronic-Obstructive

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.

Topics: 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

Invariant natural killer T (iNKT) cells may play an important role in regulating the innate and acquired immune systems in chronic obstructive pulmonary disease (COPD). However, there is little information regarding the potential role of iNKT cells in the pathogenesis of COPD. To investigate whether iNKT cells have an important role in COPD, the frequency of iNKT cells in peripheral blood of patients with COPD was analysed.. This was a comparative study of 28 patients with COPD and 19 age-matched healthy control subjects. Blood iNKT cells were stained with 6B11 mAb, anti-T cell receptor Vα24 mAb, anti-T cell receptor Vβ11 mAb or α-galactosylceramide-loaded CD1d-tetramer, and analysed by flow cytometry.. The frequency of CD4(+) 6B11(+) iNKT, CD4(+) Vα24(+) iNKT, CD4(+) Vβ11(+) iNKT and CD3(+) 6B11(+) iNKT cells was significantly lower in peripheral blood of patients with COPD than in that of healthy control subjects. The frequency of CD4(+) 6B11(+) iNKT cells was significantly lower in patients with exacerbations of COPD compared with those with stable COPD.. The frequency of iNKT was decreased in peripheral blood of patients with COPD. These results strongly suggest that iNKT cells may play an important role in the pathogenesis of COPD.

Topics: Aged; Antigens, CD1; CD4 Lymphocyte Count; Female; Flow Cytometry; Galactosylceramides; Humans; Male; Middle Aged; Natural Killer T-Cells; Pulmonary Disease, Chronic Obstructive; Sex Factors