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

• Published in: Gene therapy 2017-02, Vol.24 (2), p.104-112
• Main Authors: Shin, D, Lee, G, Lee, S, Park, S, Jung, K-H, Lee, J H, Lee, J M, Kim, J-Y, Cho, J, Bae, H
• Format: Article
• Language: English
• Subjects: 38/90; 42; 42/35; 631/1647/2300/1514; 631/250/248; 631/45/612/822; 631/61/51/201; 692/699/1785; 82; 82/51; Adenoviridae; Adenoviridae - genetics; Adenoviruses; Animals; Biomedical and Life Sciences; Biomedicine; Bronchus; Care and treatment; Cell Biology; Collagen; Development and progression; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - radiation effects; Female; Fibrosis; Forkhead protein; Forkhead Transcription Factors - genetics; Foxp3 protein; Gene Expression; Gene Therapy; Genetic aspects; Genetic Therapy; Genetic Vectors - administration & dosage; Health aspects; Human Genetics; Immunoregulation; Inflammation; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lung - immunology; Lung - metabolism; Lung - radiation effects; Lung diseases; Lungs; Lymphocytes T; Macrophages; Methods; Mice; Mice, Inbred C57BL; Nanotechnology; original-article; Patient outcomes; Pneumonia; Pneumonia - etiology; Pneumonia - prevention & control; Pneumonitis; Protein expression; Radiation; Radiation Pneumonitis - etiology; Radiation Pneumonitis - prevention & control; T-Lymphocytes, Regulatory - immunology; Trachea; Transcription factors; X-Rays - adverse effects
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2016.86

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.