Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state
Farzaneh Ghazavi, Jelle Huysentruyt, Jordy De Coninck, Stephanie Schulz, Sofie Martens, Behrouz Hassannia, Tim Wartewig, Tatyana Divert, Ria Roelandt, Bastian Popper, Andreas Hiergeist, Peter Tougaard, Tom Vanden Berghe, Marie Joossens, Geert Berx, Nozomi Takahashi, Adam Wahida, Peter Vandenabeele
Abstract
Significance Historically, programmed cell death by apoptosis is considered crucial for proper intestinal organogenesis and gut homeostasis. To challenge this concept, we generated caspase-3 and -7 double knockout mice specifically in intestinal epithelial cells (IECs). However, absence of apoptosis in IECs elicits neither morphological and inflammatory changes nor intestinal dysbiosis during gut homeostasis at steady state. This demonstrates the robustness of intestinal homeostasis at steady state for the absence of caspase-3/7 and shows that in contrast to caspase-8, which keeps necroptosis and associated inflammation in check, caspase-3/7–dependent apoptosis of IECs in homeostatic conditions is dispensable for normal intestinal development, immune cell composition, and microbiome control.