Cytokine Gene-Modulated Dendritic Cells Protect against Allergic Airway Inflammation by Inducing Il-10(+)Ifn-Gamma(+)Cd4(+) T Cells

Asthma is characterized by allergen-induced airway inflammation orchestrated by Th2 cells. Dendritic cells (DCs ) were found to efficiently prime naive T-helper cells. Thus , modification of DC function may be used as an ideal tool to treat allergic asthma by changing CD4(+) T-cell differentiation or suppressing Th2 development. In this study, we examined whether a DC-based vaccine can be applied to DCs modified with interleukin (IL)-10- and IL-12- expressing adenoviruses to prevent ovalbumin (OVA)-induced asthma in mice. Herein, we show that these modified DCs efficiently moderated the characteristics of asthma, including expressions of OVA-specific antibodies, airway hyperresponsiveness, eosinophilic airway inflammation, and Th2 cytokines production. Additionally, IL-10 and IL-12 gene -modified DCs enhanced the development of both T-helper type 1 (Th1) and IL-10(+)IFN-gamma(+) ( interferon-gamma) double- positive T cells in vivo. In vitro-generated OVA -specific IL-10(+)IFN-gamma(+)CD4(+) T cells inhibited the proliferation of naive CD4(+) T cells, and this suppressive effect was a cell contact- dependent mechanism. Furthermore, we showed that combined cytokine- modulated DCs could alleviate established allergic airway inflammation. Taken together, these results suggest that IL-10 and IL-12 gene- modulated DCs are effective in suppressing asthmatic airway inflammation through both immune deviation and immune suppression and are a potential therapeutic approach for asthma