SLE是严重危害人类健康的自身免疫病，发病机制复杂，CD40L基因的表观遗传调控异常与SLE T细胞异常活化密切相关。lncRNA是新发现的细胞内广泛转录的表观遗传调控分子，其调控免疫细胞的作用和SLE的关系受到研究者重视成为新的研究热点。我们采用lncRNA和mRNA共表达芯片筛选出SLE患者外周血CD+T细胞中差异表达的CUST124090和CD40L等多个，在此基础上我们拟深入研究CUST124090 通过CD40L调控CD+T细胞功能的作用及机制。首先通过生物信息学、RNA pull down联合质谱技术确定CUST124090通过哪些分子调控CD40L基因的表达。进一步构建慢病毒高表达或干扰表达CD+T细胞中CUST124090，探讨其对CD+T细胞功能的调节作用和机制，该研究有助于我们从表观遗传学的角度进一步明确SLE免疫学异常的发病机制，为更有效的防治SLE提供实验依据。

Systemic lupus erythermatosus (SLE) is a fatal autoimmune disease with complex etiology. Although the pathogenesis of SLE is far from clarification, abnormal epigenetic regulation on CD40L gene expression plays a pivotal role in overactivity of T lymphycytes from SLE. Long non-coding RNAs(lncRNAs), an important and new molecule of epigenetic regulation, have a genome-wide transcription in mammalians and participate in diverse important biological processes. The ralationship between the regulation of lncRNA on immune cells and the pathogenesis of SLE has attracted much reaearchers' attention and gradually became a new hotspot. In this study, we used lncRNA and mRNA coexpression array to investigate the lncRNA and mRNA expression profile of CD4+T cells in SLE, and found that several lncRNA expressions such as CUST124090 and several mRNA including CD40L were markedly increased in SLE patients. On the basis of our results, We intend to further explore the regulation of lncRNA CUST124090 on CD4+T cell function by targeting CD40L. We firstly use bioinformatic, RNA pull down and protein profiling techniques to conform the molecules combined with lncRNA CUST124090, and further construct lentiviral vector overexpressing or inhibiting lncRNA CUST124090 respectively to analyze the specific mechanisms of lncRNA CUST124090 on CD4+T cell function. The reasearch will help us to further clarify the epigenetic regulation mechanisms of Immunological abnormalities in SLE development and provide experimental basis for the disease prevention and treatment.

SLE是严重危害人类健康的自身免疫病，发病机制复杂，CD40L基因的表观遗传调控异常与SLE T细胞异常活化密切相关。lncRNA是新发现的细胞内广泛转录的表观遗传调控分子，其调控免疫细胞的作用和SLE的关系受到研究者重视成为新的研究热点。我们采用lncRNA和mRNA共表达芯片筛选出SLE患者外周血CD+T细胞中多种差异表达lncRNA及mRNA，并挑选出LncRNA-CUST124090作为研究对象，采用生物信息学分析预测出CUST124090的作用靶点为CD40L。在此基础上，我们通过体外实验，采用慢病毒构建及转染、流式细胞术、荧光定量PCR及western-blot等分子生物学技术深入研究了CUST124090 通过CD40L调控CD+T细胞功能的作用及机制。我们的研究发现：1.SLE患者CD4+T细胞中lncRNA-CUST124090及CD40L mRNA表达水平均较健康对照组显著升高，提示lncRNA-CUST1240及CD40L的异常高表达可能与SLE的发病相关；2.在Jurkat细胞系及正常人原代外周血CD4+T细胞中过表达lncRNA-CUST124090后，可显著提高CD40L的表达水平，并促进Jurkat细胞及CD4+T细胞的活化；3.在正常人原代外周血CD4+T细胞中过表达lncRNA-CUST124090后，与正常人B细胞共培养可显著提高B细胞活化水平，并促进B细胞分泌IgG。此研究有助于进一步阐明SLE的发病机制，为SLE的诊断及治疗提供新的潜在方向。