A20 controls intestinal homeostasis through cell-specific activities

Lars Vereecke, Sara Vieira-Silva, Thomas Billiet, Johan H. van Es, Conor Mc Guire, Karolina Slowicka, Mozes Sze, Maaike van den Born, Gert De Hertogh, Hans Clevers, Jeroen Raes, Paul Rutgeerts, Severine Vermeire, Rudi Beyaert and Geert van Loo ()
Additional contact information
Lars Vereecke: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927
Sara Vieira-Silva: Rega Institute, KU Leuven, Herestraat 49
Thomas Billiet: TARGID, KU Leuven, Herestraat 49
Johan H. van Es: Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Uppsalalaan 8
Conor Mc Guire: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927
Karolina Slowicka: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927
Mozes Sze: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927
Maaike van den Born: Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Uppsalalaan 8
Gert De Hertogh: University Hospital Gasthuisberg, Herestraat 49
Hans Clevers: Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Uppsalalaan 8
Jeroen Raes: Rega Institute, KU Leuven, Herestraat 49
Paul Rutgeerts: TARGID, KU Leuven, Herestraat 49
Severine Vermeire: TARGID, KU Leuven, Herestraat 49
Rudi Beyaert: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927
Geert van Loo: Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center, VIB, Technologiepark 927

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract The transcription factor NF-κB is indispensable for intestinal immune homeostasis, but contributes to chronic inflammation and inflammatory bowel disease (IBD). A20, an inhibitor of both NF-κB and apoptotic signalling, was identified as a susceptibility gene for multiple inflammatory diseases, including IBD. Despite absence of spontaneous intestinal inflammation in intestinal epithelial cell (IEC) specific A20 knockout mice, we found additional myeloid-specific A20 deletion to synergistically drive intestinal pathology through cell-specific mechanisms. A20 ensures intestinal barrier stability by preventing cytokine-induced IEC apoptosis, while A20 prevents excessive cytokine production in myeloid cells. Combining IEC and myeloid A20 deletion induces ileitis and severe colitis, characterized by IEC apoptosis, Paneth and goblet cell loss, epithelial hyperproliferation and intestinal microbiota dysbiosis. Continuous epithelial cell death and regeneration in an inflammatory environment sensitizes cells for neoplastic transformation and the development of colorectal tumours in aged mice.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms6103 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6103

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6103

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().