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Regulation of immunological balance by sustained interferon-γ gene transfer for acute phase of atopic dermatitis in mice

Gene Therapy volume 20, pages 538–544 (2013)Cite this article

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Abstract

Interferon (IFN)-γ, a potent T helper 1 (Th1) cell cytokine, is suggested to suppress Th2 cell responses. Here, we aimed to investigate whether pCpG-Muγ, a plasmid continuously expressing murine IFN-γ, is an effective treatment of atopic dermatitis, a Th2-dominant skin disease. Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) atopic mice with early dermatitis were transfected with pCpG-Muγ by a hydrodynamic tail vein injection at a dose of 0.05 or 0.2 pmol per mouse. The skin lesions improved only in mice receiving the high dose of pCpG-Muγ. IFN-γ gene transfer resulted in a high mRNA expression of IFN-γ and interleukin (IL)-12 and regulatory T cell (Treg) related cytokines, such as IL-10 and transforming growth factor-β, in the spleen, whereas it reduced the IL-4 mRNA expression, and serum levels of immunoglobulin (Ig) G1 and IgE. In addition, the gene transfer markedly inhibited the epidermal thickening, infiltration of inflammatory cells into the skin, the occurrence of dry skin and pruritus. No exacerbating effect on the Th1-mediated contact dermatitis was observed after IFN-γ gene transfer. Taken together, these results indicate that sustained IFN-γ gene transfer induced polarized Th1 immunity under Th2-dominant conditions in NC/Nga mice, leading to an improvement in the symptoms of acute atopic dermatitis without adverse side effects.

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Abbreviations

IFN-γ:

interferon γ

Ig:

immunoglobulin

IL:

interleukin

Th:

T helper.

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Acknowledgements

This work was supported in part by a Grant-in-aid for Scientific Research (B) from the Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

    K Watcharanurak, M Nishikawa, Y Takahashi & Y Takakura

  2. Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    K Kabashima

  3. Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyoto, Japan,

    R Takahashi

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  1. K Watcharanurak
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Correspondence to M Nishikawa.

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Watcharanurak, K., Nishikawa, M., Takahashi, Y. et al. Regulation of immunological balance by sustained interferon-γ gene transfer for acute phase of atopic dermatitis in mice. Gene Ther 20, 538–544 (2013). https://doi.org/10.1038/gt.2012.69

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  • DOI: https://doi.org/10.1038/gt.2012.69

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