Immune regulation of angiogenesis in inflammatory bowel diseases

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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.