目前研究已证实系统性红斑狼疮（SLE）CD4+T淋巴细胞CD70（TNFSF7）基因上调可过度辅助自身B细胞产生大量自身抗体。本课题组前期研究发现TNFSF7启动子存在DNA低甲基化和组蛋白乙酰化。CTCF是多功能转录因子，可结合低甲基化DNA片段并招募组蛋白去乙酰化酶（HDAC）。生物信息学预测CD70基因转录起始位点上游存在CTCF结合位点。我们通过Real-time PCR和Western blot检测发现CTCF在SLE患者外周血CD4+T细胞中表达显著降低，推测SLE患者CD70基因过度表达与CTCF表达下降相关。本研究拟在前期实验的基础上，探讨CTCF调控CD70基因表达的分子机制，进一步揭示CD4+T细胞中CTCF表达降低在SLE发病中的作用。本项目将有助于进一步阐明SLE发病的分子机制，并有可能为SLE的治疗提供新的思路和途径。

Overexpression of CD70 in systemic lupus erythematosus (SLE) CD4+T cells, which is associated with DNA hypomethylation and histone hyperacetylation within CD70 (TNFSF7) gene promoter, may contribute to overproduction of autoantibodies by overstimulation of autologous B cells. The multifunctional transcriptional factor CTCF has been shown to bind to some hypomethylated DNA fragment and to recruit histone deacetylase (HDAC). Bioinformatics predicted that there were CTCF binding sites at the upstream transcription initiation start site of CD70 gene. We have found that CTCF expression was significantly decreased on CD4+ T cells from lupus patients compared with healthy controls on both mRNA level and protein level. We assume that overexpression of CD70 gene is associated with less expression of CTCF. With the aim of better understanding the role of CTCF downregulation in CD4+ T cells, we will analyze the way how CTCF regulate CD70 gene expression and take a further step to the molecular pathogenesis of SLE.