LncRNA CUST65452对系统性红斑狼疮CD4+T细胞自噬的作用及机制研究

Systemic lupus erythematosus (SLE) is a fatal autoimmune disease. At present, it isn't clear about the exact mechanism of SLE immune genetic background and its cause of immune tolerance and autoimmune reaction. Recent researches have found autophagy abnormalities are closely related to the pathogenesis of SLE. Long non-coding RNA (lncRNA) as a new modification method of epigenetics, which can regulate the immune cells, has become a new research hotspot. We applied lncRNA microarray to elucidate the lncRNA expression profile.of CD4+T cells in SLE, and found that several lncRNA expressions such as CUST65452 were markedly related to the autophagy genes in SLE patients. This reasearch will be helpful for us to further clarify the epigenetic regulation mechanisms of autophagy abnormalities of CD4+T cell in SLE development and provide experimental clues for the disease prevention and treatment.

系统性红斑狼疮（SLE）是一种严重危害人类健康的自身免疫性疾病。目前对SLE免疫遗传背景及其导致免疫耐受破坏和自身免疫反应产生的确切机制尚不很清楚。近年来开展的研究表明免疫细胞自噬异常与SLE发病密切相关。长链非编码RNA（lncRNA）作为一种新的表观遗传学修饰方式，其调控免疫细胞的作用受到人们重视成为新的研究热点。我们采用lncRNA芯片筛选出SLE患者外周血CD4+T细胞中差异表达CUST65452等多个lncRNA与自噬基因相关，在此基础上本课题拟进一步探究lncRNA CUST65452调控CD4+T细胞自噬的作用和相关机制。

系统性红斑狼疮（SLE）是一种严重危害人类健康的自身免疫性疾病。目前对SLE免疫遗传背景及其导致免疫耐受破坏和自身免疫反应产生的确切机制尚不很清楚。近年来开展的研究表明免疫细胞自噬异常与SLE发病密切相关。长链非编码RNA（lncRNA）作为一种新的表观遗传学修饰方式，其调控免疫细胞的作用受到人们重视成为新的研究热点。我们采用lncRNA芯片筛选出SLE患者外周血CD4+T细胞中差异表达CUST65452等多个lncRNA与自噬基因相关，lncRNA CUST65452可部分影响CD4+T细胞ATG9A的表达，但我们的实验表明lncRNA CUST65452与ATG9A蛋白并非直接结合，可能通过其他间接途径起作用。我们发现lncRNA CUST65452与糖代谢相关蛋白PGK1、PKM、GPI和GAPDH相结合，lncRNA CUST65452可能通过调控糖代谢异常间接影响自噬相关蛋白的表达。本研究为进一步探究lncRNA CUST65452调控CD4+T细胞自噬异常奠定了基础。