异常活化的RasGRP1信号通路在过敏性紫癜发病中的作用及其机制研究

结题报告

项目介绍

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基本信息

批准号：
81301364
项目类别：
青年科学基金项目
资助金额：
23.0万
负责人：
杨柳
依托单位：
华中科技大学
学科分类：
H1202.皮肤免疫性疾病
结题年份：
2016
批准年份：
2013
项目状态：
已结题
起止时间：
2014-01-01 至2016-12-31

项目参与者：
李延；杨井；王建颖；林能兴；安湘杰；肖敏；王育珏；夏颖；韩寒；
关键词：
信号通路过敏性紫癜 RasGRP1 异常活化

项目摘要

Anaphylactoid purpura is the highest incidence of vasculitis in children. The immune factors play an important part of its pathogenesis. Our previous study showed that RasGRP1 in patients with anaphylactoid purpura in PBMC and T cells increased. And the expression of RasGRP1 in PBMC and T cells decreased using dexamethasone treatment. Different concentration dexamethasone incubation in vitro with peripheral blood T cells in patients, the expression of RasGRP1 also fell. So we speculate that the abnormal expressions of RasGRP1 play an important role in the onset of anaphylactoid purpura. We design on the carrier of virus RNA interference in vitro to decrease the expression of RasGRP1 in the patient with anaphylactoid purpura, while transfer RasGRP1 expression plasmid into normal T cells in order to increase expression of RasGRP1.The role of RasGRP1 on the pathogenesis of anaphylactoid purpura is studied by positive and negative two aspects, Furthemore, we discuss the role of the Ras signaling pathways downstream to abnormal activation of T cells. Anaphylactoid purpura mice model validation is then used to study Ras signaling pathways downstream of the molecules involved in the activation of T cells. We put forward a new interpretation of mechanism in anaphylactoid purpura and provide new ideas of its immunological therapeutic intervention. .

过敏性紫癜是儿童中发病率最高的血管炎，免疫因素是其发病的重要环节。本课题前期研究证实RasGRP1在过敏性紫癜患者外周血单个核细胞（PBMC）及T细胞中表达较正常人增高，检测使用糖皮质激素地塞米松治疗后患者外周血PBMC及T细胞中RasGRP1表达下降。同时体外使用不同浓度的地塞米松孵育过敏性紫癜患者外周血T细胞时，RasGRP1的表达亦下降。推测异常表达的RasGRP1在过敏性紫癜发病中起到重要作用。本课题设计体外以病毒为载体RNA干扰技术沉默过敏性紫癜T细胞中RasGRP1的表达，同时转入RasGRP1表达质粒进入正常人T细胞使之高表达，正反两方面研究RasGRP1在过敏性紫癜发病中的作用。探讨其作用的下游Ras信号通路导致T细胞异常活化的机制。进一步使用过敏性紫癜小鼠模型验证RasGRP1通过下游Ras信号通路分子参与T细胞的活化及其机制。为过敏性紫癜发病因素中的免疫机制提供新思路。