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银屑病中PD-1/TCR的阴阳平衡免疫学机制及芩珠凉血方的调控作用研究

银屑病中PD-1/TCR的阴阳平衡免疫学机制及芩珠凉血方的调控作用研究
  • 导航:首页 > 科学基金
  • 批准号:81673977
  • 批准年度: 2016年
  • 学科分类:中医外科(H2709) |
  • 项目负责人:缪晓
  • 负责人职称:副主任医师
  • 依托单位:上海中医药大学
  • 资助金额:57万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: 银屑病;PD-1/TCR;阴阳平衡;免疫学;芩珠凉血方
  • 英文关键词:Qinzhu Liangxue Decoction;psoriasis;PD-1/PD-L;T cell receptor

项目摘要

中文摘要

皮肤上皮细胞与结缔组织的固有免疫与适应性免疫系统的异常反馈是导致银屑病发病的重要机制。前期研究发现,芩珠凉血方可降低银屑病血热证患者的Th1 型细胞因子 IL-2、IFN-γ ,起到调节银屑病血热证 T 细胞活化的作用。我们推测银屑病是皮肤T细胞启动的“感受子”和“平衡子”(PD-1相关蛋白,阴)与“启动子”(T细胞受体(TCR)相关蛋白,阳)的失衡,芩珠凉血方可以通过启动PD-1通路、抑制TCR通路,平衡阴阳,以治疗银屑病。本项目通从临床、动物模型和细胞生物学水平上研究芩珠凉血方对银屑病关键基因表达及重要信号分子效应的调控,以诠释银屑病发生发展的免疫学机制,并从PD-1/PD-L与Th17/TCR之间阴阳平衡的效应机制探求芩珠凉血方治疗“血热证”银屑病的细胞生物学基础,对确定中医药治疗银屑病的靶点以及中医临床客观诊疗具有积极意义。

英文摘要

The skin epithelium and the connective tissue of the innate and adaptive immune system is an important cause of abnormal feedback mechanism in the pathogenesis of psoriasis. Previous studies found that Qinzhuliangxue decoction treatment reduced the blood heat syndrome and repressed the expressions of Th1 type cytokines IL-2 and IFN-γ in patients with psoriasis.of . Here we will test our hypothesis that psoriasis is a disease that imbalance between sensors/balances (such PD-1, YIN) and activators (such as TCR, YANG) in T cell activation. Qinzhuliangxue decoction treatment repressed activators such as TCR and activate balancers, such as PD-1 to rebalance the T cells in skin to treat psoriasis. Specifically, in psoriasis mouse models and cellular studies will be performed to test our hypothesis. Some translational research will also be performed. In mouse models studies, imiquimod-induced mouse model of psoriasis will be used to identify the balance between PD-1 and TCR in psoriasis development and the treatment effects of Qinzhuliangxue decoction. In cellular studies, conditional medium will be collected from T cell cultures and will be used to stimulate keratinocytes to identify the role of cytokine in PD-L1/2 activation and the interactions between T cells and keratinocytes. We will also collect skin samples from Qinzhuliangxue-treated patients toi monitor the changes of PD-1 and TCR in psoriasis progression and recovery and the effects of Qinzhuliangxue in PD-1/TCR balance. This project will disclose some new immunity mechanisms in psoriasis development and determine the immunology mechanisms in traditional Chinese medicine in the treatment of psoriasis. Our long-term goal is to develop new therapeutic strategies for patients with psoriasis.

评估说明

    国家自然科学基金项目“银屑病中PD-1/TCR的阴阳平衡免疫学机制及芩珠凉血方的调控作用研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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