母体变应性鼻炎对子代Foxp3DNA甲基化的影响及干预

研究提示母体变应原接触会增加子代变应性疾病的风险，表观遗传学在其中可能起重要作用，作用机制可能是改变了关键基因DNA甲基化水平，影响其表达，最终导致免疫调节失衡。Foxp3基因作为Treg细胞的重要转录因子，其表达异常与变应性疾病发生密切相关。我们在前期研究中发现变应性鼻炎患者的Foxp3DNA甲基化水平显著高于正常人群，本项目将以Foxp3基因甲基化状态作为研究靶点，观察母代小鼠变应性鼻炎对子代变应性炎症、Foxp3基因甲基化及Treg细胞功能的影响；进一步采用免疫治疗、糖皮质激素、甲基化转移酶抑制剂等干预变应性鼻炎母代小鼠模型，研究母代干预对子代变应性鼻炎的预防作用以及Foxp3DNA甲基化在此过程中的作用。本项目的完成将有助于从起源上研究子代变应性鼻炎的发生机制，并探讨在母体进行干预从而预防子代发生变应性鼻炎的可行性，为变应性鼻炎的预防提供新思路。

Recent researches suggest maternal allergen contact will increase the risk of offspring's allergic diseases in which epigenetics may play an important role.The mechanism of action may be to change the key gene DNA methylation level and to affect its expression, eventually leading to immunoregulatory imbalance. Foxp3 gene as an important transcription factor of Treg cells, its abnormal expression is closely related with allergic diseases.Our preliminary studies found that the Foxp3 gene methylation level of the patients with allergic rhinitis was significantly higher than that of the normal people.This project will observe the effect of materal mice allergic rhinitis on the Foxp3 gene methylation, Treg cell function and allergic inflammation of mice offspring. Further, we will intervene the maternal mice model by using the treatment of immunotherapy, glucocorticoids,DNA methylation transferase inhibitor and observe the preventive effect of maternal intervention on the subsequent allergic disorders in the offspring and the function of Foxp3 gene DNA methylation in this process. This project will help to understand the pathogenetic mechanism of allergic rhinitis from the origin, and to explore the possibiliy of the maternal intervention aiming at preventing the offspring from developing to allergic rhinitis,thus obtaining a new idea for the prevention of allergic rhinitis.