Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

摘要

In clinical therapy,the amount of antigen administered to achieve oral tolerance for allergic diseases is large,and the cost is a major consideration.In this study,we used tobacco plants to develop a large-scale protein production system for allergen-specific immunotherapy,and we investigated the mechanisms of oral tolerance induced by a transgenic plant-derived antigen.We used plants(tobacco leaves)transgenic for the Dermatophagoides pteronyssinus 2(Der p2)antigen to produce Der p2.Mice received total protein extract from Der p2 orally once per day over 6 days(days 0–2 and days 6–8).Mice were also sensitized and challenged with yeast-derived recombinant Der p2(rDer p2),after which the mice were examined for airway hyper-responsiveness and airway inflammation.After sensitization and challenge with rDer p2,mice that were fed with total protein extracted from transgenic plants showed decreases in serum Der p2-specific IgE and IgG1 titers,decreased IL-5 and eotaxin levels in bronchial alveolar lavage fluid,and eosinophil infiltration in the airway.In addition,hyper-responsiveness was also decreased in mice that were fed with total protein extracted from transgenic plants,and CD4^(+)CD25^(+)Foxp3^(+) regulatory T cells were significantly increased in mediastinal and mesenteric lymph nodes.Furthermore,splenocytes isolated from transgenic plant protein-fed mice exhibited decreased proliferation and increased IL-10 secretion after stimulation with rDer p2.The data here suggest that allergen-expressing transgenic plants could be used for therapeutic purposes for allergic diseases.