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Ghazavi, F.* ; Huysentruyt, J.* ; De Coninck, J.* ; Kourula, S.* ; Martens, S.* ; Hassannia, B.* ; Wartewig, T.* ; Divert, T.* ; Roelandt, R.* ; Popper, B.* ; Hiergeist, A.* ; Tougaard, P.* ; Vanden Berghe, T.* ; Joossens, M.* ; Berx, G.* ; Takahashi, N.* ; Wahida, A. ; Vandenabeele, P.*

Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state.

Proc. Natl. Acad. Sci. U.S.A. 119:e2024508119 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Apoptosis is widely believed to be crucial for epithelial cell death and shedding in the intestine, thereby shaping the overall architecture of the gastrointestinal tract, but also regulating tolerance induction, pinpointing a role of apoptosis intestinal epithelial cell (IEC) turnover and maintenance of barrier function, and in maintaining immune homeostasis. To experimentally address this concept, we generated IEC-specific knockout mice that lack both executioner caspase-3 and caspase-7 (Casp3/7 ΔIEC), which are the converging point of the extrinsic and intrinsic apoptotic pathway. Surprisingly, the overall architecture, cellular landscape, and proliferation rate remained unchanged in these mice. However, nonapoptotic cell extrusion was increased in Casp3/7 ΔIEC mice, compensating apoptosis deficiency, maintaining the same physiological level of IEC shedding. Microbiome richness and composition stayed unaffected, bearing no sign of dysbiosis. Transcriptome and single-cell RNA sequencing analyses of IECs and immune cells revealed no differences in signaling pathways of differentiation and inflammation. These findings demonstrate that during homeostasis, apoptosis per se is dispensable for IEC turnover at the top of intestinal villi intestinal tissue dynamics, microbiome, and immune cell composition.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Apoptosis ; Caspases ; Cell Death ; Mucosal Immunology ; Regeneration
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 119, Issue: 6, Pages: , Article Number: e2024508119 Supplement: ,
Publisher National Academy of Sciences
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)
Grants Fonds Wetenschappelijk Onderzoek
Deutsche Forschungsgemeinschaft
Deutsches Zentrum für Infektionsforschung
Torsten Haferlach Leuka€miediagnostik Stiftung
Ghent Gut Inflammation Group
GIGG
FWO-postdoctoral
Excellence of Science
Cancer Research Institute Ghent
Vlaams Instituut voor Biotechnologie
Chulabhorn Research Institute