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Adenovirus-mediated Foxp3 expression in lung epithelial cells ameliorates acute radiation-induced pneumonitis in mice

Gene Therapy volume 24, pages 104–112 (2017)Cite this article

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Abstract

Forkhead transcription factor 3 (Foxp3) has a critical role in regulatory T cells (Treg). There are an increasing number of researches concerning the functions of Foxp3 in other cells, including lung epithelial cells besides Treg. However, the roles of Foxp3 in lung epithelial cells remain poorly understood. To examine the potential therapeutic benefits of Foxp3 for lung inflammation, this study investigates the effect of adenovirus-mediated Foxp3 overexpression in a radiation-induced lung damage model. Foxp3-EGFP expressing adenovirus was administered by intratracheal injection three times over 14 days after focal X-ray irradiation. To evaluate effects of Foxp3 overexpression in radiation-induced lung inflammation, immune cell profiles of bronchoalveolar lavage (BAL) fluid were analyzed. Foxp3 gene-delivered mice showed significant inhibition of immune cell infiltration, such as eosinophils, lymphocytes, macrophages and neutrophils in BAL fluid. Histopathological analysis also showed that Foxp3 overexpression inhibits inflammatory cell recruitment and collagen deposition in lung tissues. In addition, expression of inflammatory and fibrosis-related genes was decreased in the Foxp3 expression adenovirus-infected group. These results suggest that Foxp3 expression in lungs holds considerable therapeutic potential for attenuating inflammation and fibrosis in radiation-induced lung injury.

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Acknowledgements

This work was supported by the Convergence of Conventional Medicine and Traditional Korean Medicine R&D program (JC and HB, HI15C0214) and the Nuclear Research and Development Program (JC, NRF-2011-0031695).

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Author notes

  1. D Shin and G Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea

    D Shin, G Lee, S Lee, S Park, K-H Jung, J H Lee & H Bae

  2. National Development Institute of Korean Medicine, Gyeongsan, Republic of Korea

    G Lee

  3. Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea

    J M Lee, J-Y Kim & J Cho

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Shin, D., Lee, G., Lee, S. et al. Adenovirus-mediated Foxp3 expression in lung epithelial cells ameliorates acute radiation-induced pneumonitis in mice. Gene Ther 24, 104–112 (2017). https://doi.org/10.1038/gt.2016.86

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