Interleukin (IL)-6 is a key cytokine in intestinal inflammation with pleiotropic functions both as a pro-inflammatory and as a regeneration-promoting factor.
While nearly all body cells express the coreceptor gp130, only few cell types (e.g. hepatocytes, some myeloid cells) express the IL-6 receptor (IL-6R). Engagement of this receptor-coreceptor system by sIL6 is called „classical signaling“. IL-6R can be cleaved together with its ligand and act on cells that only express gp130. This process is called „trans signaling“ and is thought to be a major sensitizing pathway for chronic inflammation.
However, there is evidence that classical signaling has a protective/homeostatic role in hepatic epithelial cells. The role of IL-6 in intestinal epithelial cells is not fully understood.
We aim to investigate the role of classic and trans-signalling IL-6 in the pathogenesis of IBD and during intestinal wound healing and to identify molecular patterns and signaling pathways by which regeneration and increased proliferation rates are mediated.
At first we will study epithelial wound healing in an in-vitro approach to identify cytokines which have a high impact on epithelial proliferation and wound closure. For that we will use a simple lesion model. To investigate certain pathways, we will use different cytokine stimuli and perform molecular analysis. In a second step, we aim to validate our results by using grown organoid cell cultures from isolated murine stem cells and finally to transfer our experiments into the living organism to collect in-vivo data.