Our project deals with basic mechanisms underlying the functional and molecular regulation of the intestinal immune system. During the first funding period a set of maker genes specific for regulatory T cells has been identified. The relevance of these genes for mucosal immune regulation in the gut has been demonstrated in a transgenic mouse model for intestinal inflammation that has been established in our lab. Whereas our main emphasis of the first funding period was the functional and molecular characterization of mucosal T cells, we next will address the role of intestinal epithelial cells (IEC) and dendritic cells (DC) for the pathogenesis of chronic intestinal inflammation and the induction of peripheral T cell tolerance. To this end, IEC and DC will be isolated from the intestine of healthy and diseased mice and subsequently characterized regarding their phenotype and function. In addition, comprehensive gene expression profiling on IEC will be performed to identify epithelial response genes, which afterwards are to be functionally characterized in vitro as well as in vivo.

Within the last funding period we have demonstrated that recombinant E. coli NISSLE 1917 represents a safe carrier for therapeutic molecules. Based on these results we will use this probiotic as carrier organism to target immunomodulatory molecules to the gut of mice suffering from chronic or acute intestinal inflammation. This approach aims to increase our understanding of immunoregulation in the gut and therefore to build the basis for rational therapeutic intervention into the processes leading to intestinal inflammation. Currently we are also working on the strategies dealing with the inducible expression of proteins in the gut mucosa. In this context the next funding period will be used to establish and test strategies for the expression of Cre-recombinase specific in the gut. .