Project Area A08
Induced intra-epithelial lymphocytes (iIELs) are widely distributed within the intestinal epithelial cell (IEC) layer. However, differentiation and function of iIELs in healthy individuals and their role within the pathogenesis of inflammatory bowel diseases (IBD) await to be fully elucidated. We found that selected deficiencies within the conventional DC (cDC1) compartment result in distinct iIEL pool […]
Project Area A07
Our project aims on an improved understanding of the regulation of prenylation within intestinal epithelial cells (IECs) and its function in epithelial integrity in the context of inflammatory bowel diseases (IBD). We will investigate molecular mechanisms regulating epithelial prenylation in order to experimentally validate our key hypothesis that the inflammation-dependent alteration of prenylation in IECs […]
Project Area A06
The intestinal vascular system exerts a critical barrier function during inflammatory bowel diseases (IBD). IFN-gamma is an important pathogenesis factor in IBD with potent vascular-directed activities. The principal aim of the project is to elucidate the molecular mechanisms by which the activation of vascular endothelial cells by IFN-gamma impairs vascular barrier functions and disturbs the […]
Project Area A05
Oncostatin M (OSM) is a highly expressed cytokine in IBD and high pretreatment expression is strongly associated with failure of anti-TNF-a therapy. OSM promotes intestinal inflammatory pathology and genetic deletion or pharmacological blockade of OSM significantly attenuates colitis in mice. Our hypothesis is that OSM acts as an inflammatory amplifier and driver of disease chronicity […]
Project Area A04
Intestinal epithelial cell (IEC) homeostasis during IBD can be facilitated by increased expression of cytokines, such as tumor necrosis factor-α (TNF-α), and by toll-like receptor (TLR) ligands derived from microbiota. However, the mechanisms of immune system-mediated tissue repair in IBD remain elusive. We have previously found that anti-TNF-α therapy induced IEC restitution is mediated by […]
Project Area A03
Central mediators of prototypical type 2 responses such as IL-33 are upregulated in the mucosa of patients with IBD, but how type 2 responses may drive pathological features of IBD or vitally contribute to the protective tissue response to damage still remains ill-defined. In this proposal, we aim to comprehensively address, how IL-33 production and […]
Project Area A02
Despite the fact that interferons (IFNs) act at mucosal surfaces, limited knowledge is available on the molecular mechanism of their mucosal functions. Our unpublished data suggest a major contribution of IFN-induced programmed necrosis to the pathogenesis of intestinal inflammation. Accordingly, IFNs promote non-apoptotic epithelial cell death, upregulation of mixed lineage kinase domain-like protein and loss […]
Project Area A01
It is well recognized that innate and adaptive immunity are inappropriately activated in inflammatory bowel diseases (IBD) and promote tissue destruction. Innate mechanisms protecting intestinal epithelial cells have been recently identified but are less well understood. We will dissect the mechanisms leading to IL-22-mediated epithelial protection, granuloma formation and granuloma-mediated epithelial barrier repair program in […]