Graves病（GD）是一种多基因遗传自身免疫性疾病，病因尚未明了，当前研究热点侧重基因遗传及免疫紊乱的致病机制。我们前期工作发现IL-10基因启动子多态性位点与GD及Graves眼病（GO）发病风险相关，并且IL-10在GD及GO中表达升高，提示IL-10可能是GD发生的重要易感基因（见工作基础）。近年来研究表明在GD的发生发展中IL-10及CD4+CD25+调节性T细胞（Treg）是重要的免疫调节因子，本研究在进一步确定IL-10基因多态性及其作为抗炎因子在GD中的作用基础上，探讨IL-10调控Treg细胞炎症反应的分子机理，及其对重要转录因子Foxp3的信号调节通路的影响，并建立具有自身免疫特性的GD甲状腺滤泡细胞和T淋巴细胞体外复合培养细胞模型，探讨IL-10及Treg细胞调控甲状腺滤泡细胞自分泌及旁分泌相关细胞因子介导免疫耐受的机制，为GD有效防治提供新思路和药物作用的新靶点。

Graves' disease (GD) is the most common organ-specific autoimmune disorder with multiple genetic predispositions characterized by reactivity to self-thyroid antigens and lymphocytic infiltrate within the thyroid. The hereditary susceptibility and immune complex deposition are believed to contribute to this disease, but its etiology remains unclear. There is strong evidence that the members of the interleukin family have participated in mediating inflammation, which may affect the outcome of patients with GD. We previously found that the single nucleotide polymorphisms (SNP) of many Interleukin genes were associated with GD and Graves' ophthalmopathy (GO) susceptibility in Chinese population. Especially, the IL-10 gene was the most significant one, and the serum level of IL-10 were increased in GD and GO patients, which suggested that IL-10 gene may contribute to GD development (In the work basis). A large body of recent studies have highlighted the importance of pathogenesis induced CD4+CD25+Treg cells and IL-10 in immuno-suppression in Graves' disease. So on this study, we firstly investigate the definite role of gene polymorphism and anti-inflammatory activity of IL-10 in Graves' disease. According to the genetic analysis of wild type and mutant reporter plasmids of the IL-10 gene transcription activity, we know the phenotype-genotype correlation of IL-10 with molecular genetic of Graves' disease. Secondly we study the quantity of CD4+CD25+Treg cells in peripheral blood of Graves'disease and explore the mechanisms of the potential regulatory role of IL-10 on CD4+CD25+Treg cells. So, we enrolled about 200 cases of Various stages of GD patients and healthy donors as normal controls, detected The proportions of CD4+CD25+Treg cells by flow cytometric analysis and immunosuppression activity by 3H-TdR.Then by investigating the effect of Transforming growth factor-β (TGF-β), associated signaling on the expression of forkhead box protein-3 (Foxp3), and a selective IL-10 siRNA, we know whether IL-10 signals is needed to maintain expression of the Foxp3 and suppressive function of Treg cells. Finally, we establish an in vitro experimental model of Thyroid follicular cells (TFCs) and CD4+CD25+T lymphocyte cells by co-culture technique. In this model, T-cell mediated inflammatory responses of thyroid follicular cells were regulated by using the skills of Real-time PCR and ELISA to detect the cytokines such as IL-2、6、10, IFN-γ and TGF-β secretion. Thyroid hormones production and thyroglobulins (Tg) release were analyzed by radioimmunoassay. It is of important value to study the role of IL-10 and Treg cell signals in immune regulation, for the illustration of immunological pathogenesis and exploration of new means to immune intervene in Graves' disease.