Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+ IFN-γ CD4+ T cells

C. Y. Hsu, S. J. Leu, B. L. Chiang, H. E. Liu, H. C. Su, Y. L. Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1011-1021
Number of pages11
JournalGene Therapy
Volume17
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • adenoviruses
  • asthma
  • dendritic cells
  • IL-10
  • IL-12
  • T cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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