| Summary: | 碩士 === 國立臺灣大學 === 免疫學研究所 === 91 === The dysregulation of allergen-specific immune response plays a central role in pathogenesis of allergic diseases. This kind of dysregulation happening in the airway would induce activation and proliferation of eosinophils, mast cells, and epithelial cells, leading to tracheal inflammation, contraction and damage. In a long term of speaking, these result in asthma. Oral administrated protein antigen would be presented by intestinal lymphoid tissue, which can induce a group of antigen-specific regulatory T cells to suppress antigen-specific immune response. This is called “Oral tolerance”. However, the application of oral tolerance mechanism for the treatment of allergy may be limited when candidate allergen can only be expensively produced by conventional systems in quantities sufficient for clinical studies. In order to solve this problem, we hope to develop a large scale protein production system for allergen-specific immunotherapy. So we generated the major allergen, house dust mite Dermatophagoides pteronyssinu (Der p) 2-transgenic plants. Conveniently oral delivery and inexpensive large scale protein production process are the advantages of transgenic plant. Then, Der p 2 generated from E. coli., yeast or transgenic plant were fed to a Der p 2-sensitized asthma murine model to investigate the application of oral tolerance induction as therapy for allergic airway inflammation.
In this study, oral feeding with low dose of Der p 2 generated from E. coli., yeast or transgenic plant would decrease Der p 2-specific IgE or IgG1 titers following immunization. The airway hyperresponsiveness were also reduced in recombinant Der p 2 fed mice compared to that of positive control group. Der p 2-transgenic tobacco total extracted protein fed mice had significantly decreased eosinophils infiltration compared to that of positive control group and decreased lymphocytes infiltration in the lung compared to that of wild type tobacco extraction fed positive control group. Other immunological tolerance indexes such as alleviated proliferation and IL-10 secretion upon antigen stimulation of splenocytes were also observed.
Our data suggested that low dose of Der p 2 proteins were capable to induce oral tolerance in an allergic airway inflammation murine model. Furthermore, there are more experiments should be done to investigate the mechanism of oral tolerance induction in the future. Conclusively, this study indicated that oral delivery of allergen proteins might be a feasible approach for the treatment of allergic diseases.
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