Tumor necrosis factor (TNF) is a multifunctional cytokine involved in many physiological and pathological processes and it exerts its function by binding to two receptors TNFR1(p55) and TNFR2(p75). Current therapies for TNF-mediated pathologies, such as inflammatory bowel disease (IBD) and arthritis, involve blocking all TNF-signaling by inhibition of TNF itself. While anti-TNF therapy has led to great successes and remarkable improvement in qaulity o flife for patients, there are unwanted side-effects e.g. increased risk for infections and therapy induced autoimmune symptoms. One possibility to improve the current TNF-target therapy, which will be investigated in this project, is the selective inhibition of TNFR1. by leaving the often regulatory TNFR2 signaling untouched, TNFR1-directed therapy might become a safer and broader applicable alternative to current anti-TNF therapies. MOreover, I expect that specific TNFR1 inhibition will allow the treatment of additional diseases where TNFR2 signaling leads to a beneficial outcome e.g. mulitiple sclerosis.