肠杆菌科可通过Th17细胞激活免疫应答，调节Th17/Treg细胞平衡是微生物与自身免疫疾病相关研究的新发现，申请人前期发现口腔菌群可侵入口腔扁平苔藓（OLP）局部病损区黏膜固有层，肠杆菌科大肠埃希菌显著高表达，结合申请人既往OLP发病机制中趋化因子免疫调控的研究，提出基于TLR4/TLR5-NF-kB通路，大肠埃希菌及趋化因子介导调控OLP免疫失衡机制的假设。本项目将通过宏转录明确OLP患者口腔微生态结构变化，分析大肠埃希菌与OLP的致病相关性；通过体外实验，验证大肠埃希菌通过TLR4/TLR5--NF-kB通路诱导趋化因子等免疫相关分子分泌，并分析大肠埃希菌、趋化因子及受体、Th17和Treg细胞相关分子三者间的关系；构建口腔感染大肠埃希菌小鼠模型，从体内水平探究大肠埃希菌定植口腔对局部黏膜和外周免疫系统的影响，为阐明口腔扁平苔藓免疫失衡机制提供新思路。

Enterobacteriaceae can activate immune response through Th17 cells, and regulation of Th17/Treg cells balance is a new discovery in microbiology and autoimmune diseases. The applicant found that oral microbes could invade the lamina propria of the local lesion area of oral lichen planus (OLP) and the Escherichia coli was significantly high expression. Combined with the study of chemokine immunoregulation in the pathogenesis of OLP in the past, the applicant proposes the hypothesis that Escherichia coli and chemokines can regulate the immune imbalance of OLP based on TLR4/TLR5--NF-kB pathway. This project will firstly identify the oral microecological structure changes in OLP patients and analyze the pathogenicity of Escherichia coli and OLP by metatranscriptomic sequencing; Then, we will confirme that Escherichia coli can induce the secretion of chemokines and other immune-related molecules through the TLR4/TLR5--NF-kB pathway; and analyze the relationship between Escherichia coli, chemokines and Th17/Treg cells-related molecules in vitro experiments.Finally, we will construct the mouse model of oral infection with Escherichia coli to explore the effect of Escherichia coli colonization on local mucosa and peripheral immune system in vivo. The study aims to provide new ideas for elucidating the immune imbalance mechanism of oral lichen planus.