共生菌调控树突状细胞对变应性鼻炎的作用及机制

Allergic rhinitis(AR）was a kind of allergic disease that was caused by the contactation of allergen which then leads to the increasing of IgE.It's critic to find a way to control AR for it's refractory symptoms. The "hygiene hypothesis" in the development of allergic diseases gained much attention in recent years. The use of antibiotics or lack of microbio stimulation in the early childhood was proved to cause higher incidence of allergic diseases, while the application of certain probiotics may reduce the incidence of allergic diseases, or alleviate the symptoms. Our previous study proved that mice raised in normal eviromrent showed lower incidence of AR than those raised in germ-free enviroment.Based on our previous research,We take the Metagenomics to detect the diference of species and quantity between the AR group and the normal group for analying the target bacteria;the human DCs were seperated and cultured with for searching the change of the fountion and the markers of this cell.Then ,the TLR antibodies were blocked and the response cell of DCs ,which called Treg cells were evaluated for the sake of finding the possible mechanism of the effects; We inject mices with the target bacteria at the different period to observe the variation of the DCs and the effect of the bacteria for AR.This research may provide the new targets for the treatment of AR by expaining the effects of microbial ecosystem on AR through DCs and the possible mechanisms.

变应性鼻炎（Allergic rhinitis，AR）是指特应性个体接触变应原后由IgE介导的、多种免疫细胞和细胞因子参与的鼻粘膜非感染性炎症性反应。近年来，"卫生学说"在变应性疾病中的作用成为研究的热点，学说认为早期缺乏微生物刺激，变应性疾病的易感率增高。我们前期研究也证实自幼在普通环境中饲养的小鼠较清洁环境中饲养的小鼠AR的发病率明显下降。为探讨共生菌与AR的关系，本研究拟利用宏基因组学检测AR人群和正常人群鼻腔菌群种属和菌量的差异，分析目标菌群；将灭活目标菌与人源树突状细胞（DCs）共培养，检测DCs相关因子，并通过阻断TLR受体，观察效应T细胞及相关因子的变化，研究其可能的作用机制；将目标菌及其成分在不同的时间点作用于幼鼠，观察小鼠外周血DCs相关因子的变化及AR的发病情况。通过该研究拟阐明共生菌通过DCs作用于AR的具体机制，为AR的防治提供新靶点。

变应性鼻炎是由炎症介质介导的I型变态反应，在欧美等发达国家的发病率明显高于其他欠发达国家，出现这一现象的原因无法单独用种族差异或基因遗传等因素解释。有学者认为，生活环境中微生物多样性的减少可能与某些免疫性疾病和慢性炎症疾病的发病率升高有关。.本课题通过运用16S rDNA方法检测AR患者鼻腔的微生态菌群的改变，并且将筛选得到的特异性细菌与人抗原提成细胞树突状细胞共培养。实验结果发现解没食子链球菌、奈瑟菌和噬盐单胞菌在AR患者鼻腔内的数量显著高于正常人群，假白喉棒状杆菌在AR患者鼻腔内的数量显著低于正常人群。解没食子链球菌可促进未成熟的树突状细胞向成熟的树突状细胞转化，具有刺激CD4+T淋巴细胞增殖的能力；抑制CD4+T淋巴细胞分泌IFN-γ的表达量，促进CD4+T淋巴细胞分泌IL-4的表达量。假白喉棒状杆菌可显著抑制解没食子链球菌诱导的未成熟的树突状细胞向成熟的树突状细胞转化。观察特异细菌对树突状细胞功能的影响，进一步揭示鼻腔菌群影响AR发病可能的作用及机制。