FcεRI-TLR2交互通过mTOR-糖酵解途径调控特应性皮炎炎症性树突状表皮细胞功能的机制研究

同时表达IgE高亲和力受体（FcεRI）和Toll样受体2（TLR2）的炎症性树突状细胞（IDEC）在特应性皮炎（AD）的发展和维持中起重要作用，但调控其功能表型的分子机制尚不清楚。研究表明，不同刺激信号诱导树突状细胞（DC）糖酵解重新编程和哺乳动物雷帕霉素靶蛋白（mTOR）介导的代谢通路决定着其功能特性。基于前期基础，我们推测来自微环境中由FcεRI和/或TLR2介导的刺激信号使得IDECs发生不同的能量代谢模式转化，从而表现出不同功能表型的差异激活，最终导致不同T细胞亚群分化和AD的慢性化进程。本课题从寻找影响FcεRI+IDECs功能的关键环境线索入手，探讨FcεRI和TLR2交互调控IDECs糖酵解和mTOR代谢通路的方式、结果和分子机制，为进一步阐明IDEC参与AD变态反应炎症的维持和/或加重的分子机制，并为通过干预IDEC能量代谢治疗AD提供新策略和新靶点。

Inflammatory dendritic epidermal cell (IDEC) that express both the IgE high affinity receptor (FcεRI) and the toll-like receptor 2 (TLR2) play an important role in the development, and maintenance of allergic inflammation in atopic dermatitis (AD). Studies have shown that glycolytic reprogramming of dendritic cells (DC) induced by different stimulus signals and mammalian target of rapamycin（mTOR）pathway-driven anabolism determine their functional characteristics. On the basis of previous work, we speculated that the stimulation signals mediated by FcεRI and/or TLR2 in the microenvironment caused IDEC to transform into different energy metabolism patterns, thus showing the differential activation and different functional phenotypes, which eventually led to the differentiation of different T cell subgroups and the chronic process of AD. This topic aimed to look for the key environmental clues involved in the functions of FcεRI+ IDECs, and to focus on crosstalk between the FcεRI and TLR2 through glycolysis and mTOR metabolic pathways and underlying molecular mechanisms. These rusults will further clarify how IDEC participate in the maintaining and/or aggravating AD allergic inflammation, and to provide the treatment of strategies and targets by intervening the energy metabolism in IDEC.