Caspase-8–dependent gasdermin D cleavage promotes antimicrobial defense but confers susceptibility to TNF-induced lethality

Authors: Benjamin Demarco, James P. Grayczyk, Elisabet Bjånes, Didier Le Roy, Wulf Tonnus, Charles‐Antoine Assenmacher, Enrico Radaelli, Timothée Fettrelet, Vanessa Mack, Andreas Linkermann, Thierry Roger, Igor E. Brodsky, Kaiwen Chen, Petr Brož - Science Advances 2020 cited by 246

defense. Last, we show that caspase-8 dimerization and autoprocessing are required for GSDMD cleavage, and provide evidence that the caspase-8 autoprocessing and activity on various complexes correlate with its ability to directly cleave GSDMD. These findings reveal GSDMD as a potential therapeutic target to reduce inflammation associated with mutations in the death receptor signaling machinery.