Immune regulation of angiogenesis in inflammatory bowel diseases

炎症性肠病血管生成的免疫调节

• 批准号: 206960999
• 负责人: Professor Dr. Michael Stürzl
• 金额: --
• 依托单位: Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/206960999?language=en
• 关键词: Immune; regulation; angiogenesis; inflammatory; bowel

Inflammatory bowel diseases (IBD) are characterized by two important cell biological features, namely T-cell activation and angiogenesis. In this framework Interferon (IFN)-y is regarded as an important regulatory molecule of immune function and T-cell activation. Vascular endothelial growth factor is known as a major angiogenesis factor. Based on previous results of our group, the project focuses on two new and complementary functions of both of these major pathogenesis factors in IBD, namely the regulation of T-cell activation by VEGF and the activity of IFN-y as an inhibitor of angiogenesis. Specific goals of the T-cell directed approach are (1) to evaluate the functional role of the VEGF receptor KDR on T-cells in colitis, (2) to analyze combination effects of KDR and neuropilin-1 in Tcells and (3) to prove the relevance of KDR-expression in T-cells for pathogenesis of human IBD. The vascular branch of the project will target to dissect the combination effects of IFN-y and VEGF on (4) blood vessel function in expenmental colitis models in mice and (5) at the molecular level in blood vessel endothelial cells isolated from inflammatory bowel disease tissues of humans. It is the common goal of this project to exploit the obtained results for the development of new strategies for combination therapy of IBD.

炎症性肠病（IBD）的特征在于两个重要的细胞生物学特征，即T细胞活化和血管生成。在这个框架中，干扰素（IFN）-γ被认为是免疫功能和T细胞活化的重要调节分子。血管内皮生长因子是一种重要的血管生成因子。基于我们小组以前的结果，该项目侧重于IBD中这两个主要致病因素的两个新的和互补的功能，即VEGF对T细胞活化的调节和IFN-γ作为血管生成抑制剂的活性。T细胞定向方法的具体目标是（1）评估VEGF受体KDR在结肠炎中对T细胞的功能作用，（2）分析KDR和神经纤毛蛋白-1在T细胞中的组合作用，和（3）证明T细胞中KDR表达与人IBD发病机制的相关性。该项目的血管分支将致力于剖析IFN-γ和VEGF对（4）小鼠实验性结肠炎模型中的血管功能和（5）从人的炎症性肠病组织分离的血管内皮细胞中的分子水平的联合作用。本项目的共同目标是利用所获得的结果开发IBD联合治疗的新策略。