Dendritic cells subsets in an acute model of cigarette smoke induced lung inflammation

Introduction: Cigarette smoking (CS) is the main risk factor for the development of inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD). The lung inflammatory response to CS exposure is more complex than neutrophil accumulation. However, targeting the acute effects of CS-mediated pulmonary inflammation could be considered as a possible therapeutic approach in COPD. Several inflammatory cells from both the innate and adaptive immune system, together with their mediators, participate in the inflammatory response of COPD. The inflamed airways of COPD patients contain inflammatory cells including neutrophils, macrophages, T lymphocytes and dendritic cells (DCs). The relative contributions of these inflammatory cells to airway injury and remodeling are not well documented. In particular, the potential role of DCs as mediators of inflammation in the smoker's airways and COPD patients is poorly understood. In the current study, we investigated the relaive role of DC subsets in an acute models of CS induced airway inflammation. Materials and Methods: Balb/c mice, were divided to 4 groups, a) mice were exposed for 5 days with CS, b) were injected once daily with 10μg of Flt3L (to expand DC in vivo) or with serum albumin (0.01 % in PBS) for 10 consecutive days, combined with CS exposure from day 6-10, c) were treated with 200 μg of 120g8 Abs or as a control with 200 μg of rat IgG for 4 consecutive days starting 1 day before CS, d) were either injected daily with Flt3L from day 0 for 10 consecutive days and with 120g8 from day 5 for 4 consecutive days starting 1 day before CS exposure. Results: Flt3L, significantly elevated KC, IL-6, MIP-1α, IL-12 and IL-10 production, but diminished IL-17 production. Modulation of DCs by Flt3L and 120g8 Abs decreased the number of inflammatory cells in BAL possibly by the release of IL-10 and inhibition of IL-17 production in smoke-exposed mice. Conclusion: We found a novel mechanism linking DCs with neutrophils and alveolar macrophages infiltration in the early stage of smoke induced inflammation, mainly by the alteration of mediator release and adhesion molecular expression. Moreover, pDC play a role in the accumulation of alveolar macrophage and CD103+DC in lung parenchyma.