https://scholars.lib.ntu.edu.tw/handle/123456789/196097
Title: | Cytokine Gene-Modulated Dendritic Cells Protect against Allergic Airway Inflammation by Inducing Il-10(+)Ifn-Gamma(+)Cd4(+) T Cells | Authors: | HSU, CHIH-YU LEU, SY-JYE CHIANG, BOR-LUEN |
Keywords: | asthma;dendritic cells;adenoviruses;IL-10;IL-12;T cells | Issue Date: | 2010 | Journal Volume: | v.17 | Journal Issue: | n.8 | Start page/Pages: | 1011-1021 | Source: | GENE THERAPY | Abstract: | 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. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/235510 |
Appears in Collections: | 醫學系 |
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