IL-9/IL-9R通路介导记忆性B细胞功能异常参与原发性肾病综合征（PNS）低IgG血症发生

原发性肾病综合征（PNS）是我国儿童终末期肾病重要病因之一，血浆IgG显著降低是致PNS继发免疫功能低下的重要原因，与本病易发生感染、甚至致死性感染以及（频）复发密切相关。课题组在上一个自然科学基金资助下，研究发现PNS外周血记忆性B细胞分泌IL-9、IgG+记忆性B细胞、分泌IgG浆细胞水平降低，结合本病发病特点及免疫相关机制研究进展，提出科学假说：儿童PNS发生、发展及疾病复发过程中，记忆性B细胞通过IL-9–IL-9R/STAT3信号通路，致其向分泌IgG的浆细胞分化过程受损，参与了PNS低IgG血症的发生。本课题拟通过体内外实验，研究记忆性B细胞向分泌IgG的浆细胞分化过程及其调控机理，进而探讨参与PNS低IgG血症发生的免疫学机制，以期通过细胞、动物干预研究为临床调控PNS免疫功能低下寻找新的治疗手段、并改善预后减少终末期肾病的发生。

Primary nephrotic syndrome (PNS) is one of the important causes of end-stage renal disease in children in China. Significant reduction in serum IgG is a main cause of secondary immune dysfunction in course of disease, and it is also closely associated with secondary infection, fatal infection and even frequent recurrence in PNS patients. Based on the former research that supported by Natural Science Foundation, our team found the levels of IgG+ memory B cells and IgG-secreting Plasma cells in peripheral blood of children with PNS significantly decreased. Combined with recent research progress on characteristics and immune-related mechanisms of childhood PNS, we assumed that IL-9-IL-9R/STAT3 signaling pathway is impaired, and resulting in blocking of differentiation of memory B cells to IgG-secreting Plasma cells and the reduction of serum IgG levels in PNS patients. To find the potential immunological mechanisms of the low IgG in childhood PNS, we intend to study the differentiation process of memory B cells into IgG-secreting plasma cells and its regulatory factors through in vitro and in vivo experiments, and further explore a new therapeutic method for low IgG and reduce the incidence of end-stage renal disease in childhood PNS patients through cell and animal intervention researches.