The role of metalloprotease activity in necroptosis driven inflammation (A03)

• Subject Area: Immunology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 414786233

In the last funding period, we were able to show, using necroptosis as an example, that lytic cell death results in the switch-like activation of ADAM17, leading to the maturation of membrane-bound TNF. In vitro, this phenomenon represents the central mechanism for activation of proinflammatory signal transduction of neighboring cells. We will now investigate how necroptosis affects translation of pro-TNF and whether this mechanism also applies to other proinflammatory processes. We will also explore whether other pro-inflammatory substrates are activated by this process and how activation of ADAM17 occurs. We also plan to characterize this phenomenon in vivo, with particular focus on the species specificity of caspase-8.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1403: Cell Death in Immunity, Inflammation and Disease
• Applicant Institution: Universität zu Köln
• Project Head: Professor Dr. Veit Hornung