AIT是甲减、桥本脑病、不良妊娠结局及影响后代智力发育的危险因素。近年来发现VitD缺乏与AIT密切相关。Th17/Treg轴失衡、耐受型DCs数量与功能异常是AIT的重要机制。前期研究证实补脾益气法能调控AIT小鼠Th17/Treg轴平衡，“脾失之卫”是AIT的关键病机。VitD代谢通路相关DNA甲基化使VitD生物效应降低，分别通过PI3K/Akt/mTOR和VDR/PLC-γ1/TGF-β1通路导致DCs成熟和Th17/Treg轴失衡。本课题以VitD代谢通路相关酶及VDR-RXR DNA甲基化为切入点，围绕PI3K/Akt/mTOR和VDR/PLC-γ1/TGF-β1两个通路，利用焦磷酸测序等技术初步阐明AIT“脾失之卫”的关键途径、环节及分子机制，揭示补脾益气法的效应机制，丰富“脾为之卫”理论内涵，为防治AIT提供新的研究策略和实验依据。

Autoimmune thyroiditis is a risk factor for hypothyroidism, Hashimoto’s encephalopathy, adverse pregnancy endpoints and impaired brain development.Vitamin D deficiency is tightly related to AIT recently.The disbalance of Th17/Treg axis and altered proportion and function of tolerogenic DCs is closely related with AIT.The method of invigorating the splenic Qi is proved to regulate the balance of Th17/Treg axis in AIT mice by our group. ‘The spleen loses the defensive function’is the key pathogenesis of AIT. The DNA methylation of vitamin D related enzymes and VDR-RXR is proved to reduce the biological function of vitamin D, hence inducing the growth-up of DCs and imbalance of Th17/Treg axis through PI3K/Akt/mTOR and VDR/PLC-γ1/TGF-β1 pathways respectively. This project will clarify the key points and molecular mechanism of ‘The spleen loses the defensive function’ of AIT mice, reveal the therapeutic mechanism of the method of invigorating the splenic Qi, enrich the the theory of ‘The spleen has the defensive function’ and offer the strategies and experimental basis for the treatment of AIT through studying the DNA methylation of vitamin D related enzymes and VDR-RXR and PI3K/Akt/mTOR and VDR/PLC-γ1/TGF-β1 pathways with pyrosequencing methods.