炎症状态下B淋巴细胞糖基化酶表达低下引起的IgA糖基化缺陷是IgAN的关键发病机制。miR-155能调节T淋巴细胞分化及B淋巴细胞糖基化酶的功能。研究发现IgAN患者外周淋巴细胞miR-155表达显著低于正常对照。我们推断IgAN患者中miR-155的低表达能影响T细胞分化，使Th2细胞增加，Treg细胞减少，产生大量细胞因子，促使B淋巴细胞分泌大量IgA，抑制糖基化酶表达和功能，导致IgA分子异常糖基化加重，形成多聚IgA，沉积于肾脏组织引起IgAN。因此升高miR-155表达可能是治疗IgAN的潜在方法。本项目将明确miR-155对IgAN患者外周血和扁桃体T淋巴细胞分化、B淋巴细胞糖基化酶表达、IgA分子糖基化水平的调控作用，并通过体内和体外干预实验探讨上调miR-155表达作为IgAN新治疗靶点的疗效。一方面加深对IgAN发病机制的认识，另一方面初步探索基因治疗IgAN的可行性。

Dys-glycosylation of IgA caused by low expression of glycosylation enzymes in B lymphocytes under inflammatory circumstance is one of the key pathogenesis of IgA nephropathy. miR-155 can regulate the T lymphocyte differentiation and function of B lymphocyte glycosylation enzymes. Our research indicated that the miR-155 expression level in peripheral lymphocytes of IgAN patients is significantly lower than normal controls. It is speculated that the lower expression of miR-155 in IgAN patients affects the T lymphocyte differentiation, increases the Th2 cells, decreases the Treg cells, produces many cytokines, enhances the IgA secretion of B lymphocytes, inhibits glycosylation enzymes, causes severe aberrant IgA glycosylation, forms polymeric IgA which deposits in kidney tissues, and finally leads to IgAN. Therefore, up-regulation of miR-155 may be a potential treatment of IgAN. In this project, we will clarify the effect of miR-155 on regulation of peripheral and tonsil lymphocytes in T cell differentiation, B cell glycosylation enzyme expression as well as IgA glycosylation level. The potential of up-regulation miR-155 as a novel treatment for IgAN will also be tested in vitro and in vivo. Through this study, a better understanding of IgAN pathogenesis will be gained and feasibility of novel gene therapy for IgAN will be verified.