系统性红斑狼疮（SLE）是一种危害人类健康的多系统受累的自身免疫性疾病，其发病机制尚不明确。大量研究表明可能与基因的易感性和环境因素引起的T细胞异常有关，如异常分化活化的滤泡型辅助T（Tfh）细胞 。最近研究发现高盐饮食可诱导Th17细胞从而促进自身免疫疾病的发展进程。本项目前期工作发现高盐（NaCl）能明显加重狼疮小鼠狼疮样表型、升高Tfh细胞比例、降低CD4+T细胞基因组整体DNA甲基化水平。由此，我们推测高盐能促进狼疮发展，其分子机制可能是：NaCl降低CD4+T细胞中某些基因的DNA甲基化水平，从而促进Tfh细胞分化活化。本项目致力于研究NaCl通过降低何种基因的DNA甲基化水平，从而促进Tfh细胞的分化及加速SLE的发展，并在体内和体外实验中验证该基因对高盐诱导的Tfh细胞分化和狼疮表型的影响。该研究将有助于进一步揭示SLE的疾病发展机制，并为改善SLE病人的预后提供理论基础。

Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease with multiple system involvements. The pathogenesis of SLE remains unclear. It has been well documented that the abnormal T cells，such as abnormal follicular T helper （Tfh）cells， induced by genetic susceptibility and environmental factors contribute to the initiation and development of SLE. As a factor of environmental triggers, high salt diet has been recently revealed to promote autoimmunity by driving Th17 cells. In our previous study, NaCl is capable of promoting the progress of lupus-like syndrome in lupus-prone mice, increasing the percentage of Tfh cells and reducing the DNA methylation level of CD4+ T cells. Therefore, we hypothesize that the mechanism of high salt promoting lupus might be that NaCl promotes Tfh cell differentiation via altering DNA methylation level of CD4+T cells. Thus, this study aims to explore the target genes that are regulated by NaCl induced DNA demethylation and essential for the differentiation of Tfh cells, and in in vitro and in vivo condition, to further validate the effect of target genes in NaCl-induced Tfh cell differentiation and lupus progression. This project may reveal potential pathogenesis of SLE and provide theoretical evidence for improving the prognosis of SLE patients.