miR-122对Th17/Treg分化和功能的影响及其在银屑病发病中的作用机制

目前银屑病的病因和发病机制尚未完全阐明，CD4+T细胞的异常活化及分化在银屑病的发病中起重要作用。我们在银屑病皮损与健康对照皮肤中通过microRNA芯片与mRNA表达谱芯片技术，筛选并验证了miR-122在银屑病皮损中高表达，Bach2为其下游靶基因。最新研究发现，Bach2基因作为一种具有广泛免疫活性的关键性调节因子，通过限制多种效应性CD4+T细胞的分化，有效促进Treg细胞的形成，维持免疫系统的稳定，阻止自身免疫炎症反应的发生。由此提出科学假说：银屑病皮损中高表达的miR-122可通过调控Bach2基因的表达，影响Th17/Treg的分化和功能，打破Th17/Treg平衡，出现Th17优势反应，分泌大量的IL-17A、IL-17F和IL-22，促进银屑病的发生发展。本研究将采用细胞培养、siRNA转染、动物实验等方法进行体内外实验验证该假说，为深入研究银屑病的免疫反应异常奠定基础。

At present, the etiology of psoriasis and pathogenesis have not been fully elucidated yet, and abnormal activation and differentiation of CD4+ T cells play an important role in the pathogenesis of psoriasis. We screened and verified that the expression of miR-122 is elevated in psoriatic lesions, and Bach2 is a downstream target gene of miR-122, through microRNA microarray and microRNA expression profile microarray in psoriatic lesions and healthy skin. Recent study found that Bach2 gene， a key regulatory factor with wide immune activity , can limit the differentiation of multiple kinds of effector CD4+ T cells and promote the formation of Treg cells effectively to maintain the stability of the immune system and prevent autoimmune inflammatory response. Thus we propose the hypothesis that the elevated expression of miR-122 in psoriatic lesions can affect Th17/Treg differentiation and function by regulating the expression of Bach2 gene and break the Th17/Treg balance resulting in the advantage of Th17 which secret large amounts of IL-17A, IL-17F and IL-22 and promote the development and progression of psoriasis. In this study, both in vivo and in vitro experiments such as cell culture , siRNA transfection, animal experiments and other methods will be carried out to verify this hypothesis to lay the foundation for in-depth study of the immune response abnormalities in psoriasis.