Funding period: 01.02.2019 – 31.08.2020
The aim of this project is to investigate how the commensal gut microbiota influences PAR signal transduction and whether the barrier function of the intestine and the recruitment and development of gut-resident immune cells are modulated by a microbiota-dependent regulation of PARs. First, the expression and activity of coagulation factors and the expression of PARs in comparative analyzes of primary small intestinal epithelial cells of germ-free and colonized mice will be investigated. To investigate the functional importance of these factors in epithelial cells, epithelium-specific knock-out mice are generated using the villin-cre mouse model. These mouse models facilitate to investigate the significance of identified coagulation factors and PARs expressed by epithelial cells for the intestinal barrier and the formation of capillaries in the small intestine. In particular, it will be investigated to what extent the cytokine profile in the small intestine of epithelium-specific knock-out mice is altered in comparison to wild type control mice and whether the homeostasis of intestinal immune cells is significantly impaired by the deficiency of PARs. Taxonomic microbiome analyzes of the generated epithelium-specific knock-out mouse lines are used to investigate the influence of epithelial PAR signal transduction on the composition of the intestinal microbiome.