FoxO1/KLF2/S1P1是控制胸腺成熟T细胞从胸腺迁出发挥功能的关键。重症肌无力是自身免疫病，患者胸腺细胞和外周血T细胞亚群存在显著异常。为深入探讨其机制，本研究已通过免疫组化、流式细胞术、荧光定量PCR发现并证实胸腺细胞FoxO1、KLF2、S1P1表达与对照组存在差异，且FoxO1的下游产物CD62L、CCR7表达异常。因此，我们拟进一步通过流式细胞仪分选出CD3+CD4+CD8-和CD3+CD4-CD8+分化成熟阶段的单阳性胸腺细胞，采用FoxO1基因转染、基因沉默、FoxO1磷酸化和去磷酸化等手段调节FoxO1在细胞的表达，观察其对KLF2、CD62L、CCR7和S1P1等分子表达的影响，通过体内、外试验分析胸腺细胞输出的调控机制，在理论上揭示FoxO1/KLF2/S1P1轴在重症肌无力胸腺及外周T细胞亚群异常中的作用，寻找调控胸腺细胞输出的分子靶点，为临床疾病诊治提供依据。

FoxO1-KLF2-S1P1 axis is the critical factor in mature CD4 or CD8 single positive thymocytes(SP thymocytes) emigration from thymus. Myasthenia gravis is an autoimmune disease mediated AChR antibodies and associated with T lymphocytes. There are often abnormalities of thymocytes and blood T cells subsets in MG. To assess the relationships between the periphery T cell subsets and abnormal MG-thymus, we have found FoxO1,KLF2,CD69,CCR7 and S1P1 expression up-regulation in MG thymic tissue used by immunohistochemisty, flow cytometry and real time PCR.We'll sorting further CD3+CD4+CD8- and CD3+CD4-CD8+ SP thymocytes from single-cell suspensions of MG thymus.FoxO1 gene or siRNA for FoxO1 will be transfected into SP thymocytes.The FoxO1 expression in SP thymocytes will be regulated using gene transfection, gene silencing and FoxO1 phosphorylation, dephosphorlation. The downstream moleculars of FoxO1,such as KLF2 CD62L CCR7 and S1P1, will be analyzed using western blot. The abilities of mature SP thymocytes export from MG thymus will be observed using Transwell migration and human MG thymus grafted-SICD mice model. These discoveries will be the first detailed analysis of the FoxO1-KLF2-S1P1 axis in MG thymus and likely to result in significant therapeutic application.