Th17 细胞对鼻息肉组织中PI3K p110 δ通路的活化和自身免疫抗体的诱导作用

项目名称： Th17 细胞对鼻息肉组织中PI3K p110 δ通路的活化和自身免疫抗体的诱导作用

项目编号： No.81470673

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李华斌

作者单位： 上海交通大学

项目金额： 73万元

中文摘要： 磷脂酰肌醇3激酶（PI3K）的p110 δ同工酶对B细胞分化具有关键的调节作用，但在鼻息肉发病中的作用研究较少。最近有研究报道部分鼻息肉组织中存在自身抗体，提示自反应B细胞也参与鼻息肉发展过程。我们课题组前期研究发现国人鼻息肉存在显著的Th17细胞分化、中性粒细胞浸润及增高的抗中性粒细胞抗体，考虑到Th17细胞合成的主要细胞因子IL-17A是参与自身免疫性疾病的核心介质，我们因此推测鼻息肉中可能存在Th17细胞合成的细胞因子IL-17A、IL-21等通过PI3K δ同工酶调节自反应B细胞发育、分化的关键分子事件。为证实该假设，本项目拟检测鼻息肉中Th17细胞来源的细胞因子IL-17A、IL-21对自反应B细胞分化和活化的作用及并探讨p110 δ同工酶在该过程中可能的主导作用。这个研究有望从PI3K激酶调节自反应B细胞活化的角度阐明鼻息肉发病的新的分子机制以建立更有效的针对性治疗策略。

中文关键词： 鼻息肉；Th17细胞；信号通路；PI3K；自身抗体

英文摘要： The delta isoform of the p110 catalytic subunit (p110δ) of phosphoinositide3-kinase (PI3K) plays an essential role in B-cell development and function, but its role in the pathogenesis of nasal polyps is largely unknown. It has recently been reported that autoantibodies, particularly those against nuclear antigens, are presented in nasal polyps locally. The presence of autoantibodies suggests that the expansion of self-reactive B-cell clones may contribute to the pathogenesis of nasal polyps. In previous study, we observed Th17 response and excessive neutrophil accumulation and anti-neutrophil antibody in nasal polyps. Given Th17-typed cytokines such as IL-17A and IL-21 were found to play pivotal role in autoimmune diseases, we thus hypothesized that Th17-typed cytokines may regulate the development of self-reactive B-cells through PI3K δ-dependent pathway in nasal polyps. To address this issue, we plan to examine the effects of IL-17A and IL-21 on self-reactive B-cells in nasal polyps and assess the underlying role of PI3K p110 δ in this process. This study may elucidate a molecular mechanism of nasal polyps by detecting how PI3K p110 δ regulate the development of self-reactive B-cells, and establish an effective strategy for the treatment of nasal polyps.

英文关键词： Nasal polyps;Th17 cells;Signaling pathway;PI3K;Autoantibody