Graves病患者存在免疫耐受障碍导致机体代谢亢进，目前该病常用药物难以从根本上改善免疫耐受障碍使其复发率高。我们前期研究表明Graves病患者外周血CD19+CD24hiCD27+B细胞亚群属于调节性B细胞 (Bregs)，它是一种新发现的通过IL-10介导免疫耐受的B细胞亚群。和正常人比较，Graves病患者外周血Bregs亚群数量明显减少，IL-10的分泌水平明显降低，使其对CD4+T细胞的免疫抑制功能显著下降。 本课题将通过体外实验研究影响Graves病患者外周血Bregs数量和功能的分子机制。一方面考察其是否因为B细胞激活因子(BAFF)通过PI3K/Akt/mTOR信号转导通路调节细胞增殖的作用减弱导致数量减少；另一方面分析其是否由于STAT3磷酸化水平下降、STAT3进入细胞核内量减少导致IL-10分泌降低。该课题的研究将为Graves病的免疫治疗提供新靶点，促进新药物研发。

The loss of immunological tolerance in Graves' disease(GD) patients is pivotal to the appearance of hyperthyroidism. Commonly used drugs can not fundamentally change the impairment of immune tolerance in GD patients resulting in high recurrence rate. Our latest research disclosed the CD19+CD24hiCD27+ B cell subset in the peripheral blood of GD patients belongs to regulatory B cells (Bregs), which is a newfound B cells subpopulation and plays an immunosuppressive role via secreting cytokine IL-10. The proportion of Bregs subset and level of IL-10 secretion were significantly reduced in GD patients, which leads to serious impairment of the suppressive function on CD4+ T cells compared with healthy individuals. This project aims to study the mechanism how the quantity and function of Bregs declined in GD patients in vitro experiments. On one hand, it will be investigated if the weakened stimulating effect of B cell activating factor (BAFF) on cell proliferation through PI3K/Akt/mTOR signal pathway leads to the reduction of Bregs; On the other hand, it will be verified if the decrement of STAT3's phosphorylation level and amount in nucleus leads to the secretion reduction of IL-10 from Bregs. The study will provide an innovative target for immunotherapy of Graves' disease, thus promote the research and development of new drugs.