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

Gene Therapy volume 17, pages 1011–1021 (2010)Cite this article

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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.

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Acknowledgements

This study was supported by grants from Cathay General Hospital (95 CGH-TMU-06) and from the National Science Council of the Republic of China (NSC95-2314-B-038-052).

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Authors and Affiliations

  1. Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan, ROC

    C-Y Hsu

  2. Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC

    S-J Leu & Y-L Lee

  3. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC

    B-L Chiang

  4. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC

    H E Liu

  5. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC

    H-C Su

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  1. C-Y Hsu
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Correspondence to Y-L Lee.

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Hsu, CY., Leu, SJ., Chiang, BL. et al. Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+IFN-γ+CD4+ T cells. Gene Ther 17, 1011–1021 (2010). https://doi.org/10.1038/gt.2010.39

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