Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+ IFN-γ CD4+ T cells
Journal
Gene Therapy
Journal Volume
17
Journal Issue
8
Pages
1011-1021
Date Issued
2010
Author(s)
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-γ (interferon-γ) double-positive T cells in vivo. In vitro-generated OVA-specific IL-10 IFN-γ 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. ? 2010 Macmillan Publishers Limited All rights reserved.
Subjects
adenoviruses; asthma; dendritic cells; IL-10; IL-12; T cells
SDGs
Other Subjects
adenovirus vector; antibody; gamma interferon; interleukin 10; interleukin 12; ovalbumin; Adenovirus; animal cell; animal experiment; animal model; animal tissue; antibody blood level; article; asthma; CD4+ T lymphocyte; cell proliferation; controlled study; cytokine production; dendritic cell; drug activity; drug mechanism; female; in vitro study; in vivo study; lung lavage; nonhuman; pneumonia; priority journal; protein expression; Th1 cell; Th2 cell; Adenoviridae; Animals; Asthma; CD4-Positive T-Lymphocytes; Dendritic Cells; Female; Gene Therapy; Immunoglobulin E; Immunoglobulin G; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-12; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells; Mus
Type
journal article