CD4+T细胞亚群失稳是导致胸腺瘤型重症肌无力（TAMG）发生的重要病理基础，但机制不明；最新研究报道超级增强子相关miRNAs是调节细胞分化等的重要分子。我们发现TAMG患者CD4+T细胞中miR-155异常高表达，且与Th17亚群比例升高相关；生信分析提示miR-155具有与CD4+T细胞特异性超级增强子SE19337结合位点并潜在调控邻近基因表达。预实验发现CD4+T细胞中miR-155能正向调控邻近基因JAM2的转录，并影响Th17相关炎症因子表达，但miR-155是否通过超级增强子调控JAM2转录尚不清楚。为此，本项目拟进一步在瘤体/外周CD4+T细胞中利用ChIP-seq、TALEN等技术研究超级增强子与miR-155结合并调节JAM2的分子机制，及其对细胞亚群增殖分化等的影响；并构建SE19337基因敲除细胞在EAMG动物模型中初步探讨其功能，为该疾病防治提供特异性干预靶点。

The instability of CD4-T cell subgroup is an important pathological basis for the occurrence of thymoma-associated myasthenia gravis (TAMG), but the mechanism is not clear. Recent studies show that super-enhancer-associated miRNAs are important molecules that regulate cell differentiation. Our previous study found that miR-155 was abnormally high expression in TAMG patients' CD4+T cells and associated with in the higher proportion of CD4+Th17 cells, and the bioinformatic analysis showed that miR-155 had binding sites with CD4+T cell-specific super-enhancer SE_19337 and potentially regulated the expression of adjacent genes. Further study showed that miR-155 could positively regulate the transcription of JAM2 in CD4+T cells and affect the expression of Th17-related inflammatory factors. However, the mechanism of the miR-155 regulating JAM2 transcription mediated by super-enhancer is still not clear. In the project, we will further study the molecular mechanism by using chip-seq, TALEN and other technologies in tumor/peripheral CD4+T cells, and elucidate the effect of this pathway on the proliferation and differentiation of CD4+T cell subsets, and preliminarily explore its function in experimental autoimmune myasthenia gravis (EAMG) animal models by using SE_19337 gene knockout CD4+ T cells, in order to provide a new target for the prevention and treatment of TAMG.