尘螨肠道细菌FimH蛋白在尘螨疫苗免疫治疗中的作用及机制研究

过敏原特异性免疫疗法（SIT）是目前WHO认可的过敏性疾病唯一的对因疗法。但临床上却发现尘螨粗提物疫苗的SIT疗效远优于现有的基因工程尘螨疫苗，这是困扰变态反应领域的重要科学问题。我们前期研究发现尘螨消化道内含有多种细菌，其中肠杆菌为优势菌群，并证实商品化尘螨粗提物疫苗含有肠杆菌菌毛FimH蛋白。研究表明FimH是TLR4的重要配体，且TLR配体具有佐剂和免疫调节作用。故假设：FimH蛋白在尘螨粗提物疫苗中的天然佐剂作用，是该疫苗疗效优于基因工程尘螨疫苗的重要原因。本项目拟采用基因沉默等技术探讨FimH对DC功能的影响及其分子机制；探讨FimH对Th1型以及Tr1/Treg细胞分化的影响；联合应用FimH蛋白提高基因工程尘螨疫苗的SIT疗效。预期结果将阐明FimH蛋白在尘螨疫苗免疫治疗中的作用及其机制，为新型基因工程尘螨疫苗研发提供新方法和新理论。

Allergen-specific immunotherapy (SIT) is the only etiological therapy for allergic disease approved by WHO. However, it has been found that the SIT efficacy of dust mite crude extract (DMCE) vaccine is much better than that of the genetic engineering dust mite (DMGE) vaccine. This is an important scientific problem in the field of allergy. Our previous studies have found that there were many kinds of bacteria in the digestive tract of dust mites, among which Enterobacter was the dominant group. It was confirmed that commercial DMCE vaccine contained FimH protein of Enterobacter pili. Previous studies have shown that FimH is an important ligand of TLR4, which has adjuvant and immunoregulation effects. Therefore, we hypothesized that the natural adjuvant effect of FimH protein in DMCE vaccine is an important reason that the efficacy of DMCE is better than DMGE. This project aims to explore the effects of FimH on modulating DC function and its underlying mechanism by using gene silencing technology; the effects of FimH on Th1 and Tr1/Treg cell differentiation, and the combined application of FimH protein with DMGE vaccine to improve the SIT efficacy. The expected results will clarify the role of FimH protein in the SIT of DMCE, and provide a novel method and theory for the development of new genetic engineering dust mite vaccine.