Inflammatory bowel diseases (IBD) are chronic inflammatory disorders that cause structural damage to the intestine and may lead to various complications such as fibrosis, stenoses, fistula formation and cancer. Cytokines and soluble mediators produced by immune and non-immune cells play a fundamental role in IBD pathogenesis, as shown by the fact that cytokine (TNF, p40/p19) and cytokine signaling (JAKi) blockers are key therapeutic options for IBD patients. However, the factors driving resistance against anti-cytokine agents are poorly understood. We have screened a large biobank of IBD patients refractory to therapy and noted in these patients a marked up-regulation of tumor necrosis factor (TNF) and TNF receptor superfamily (TNFRSF) members. Specifically, TNFSF7 and TNFSF9 were strongly induced in therapy-refractory IBD patients. In this project, we want to explore the function of these proteins by taking advantage of patient samples and murine models of chronic intestinal inflammation. We aim to provide a better understanding of the role of TNF- and TNFR- superfamily members in refractory inflammatory bowel disease and to elucidate the underlying molecular mechanisms to overcome current therapeutic limitations. These findings may open new avenues for therapy of treatment-refractory IBD patients.
Principal Investigators
PD Dr. rer. nat. Dr. habil. med. Benno Weigmann