| First Author | Vereecke L | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 5103 | PubMed ID | 25267258 |
| Mgi Jnum | J:225342 | Mgi Id | MGI:5692406 |
| Doi | 10.1038/ncomms6103 | Citation | Vereecke L, et al. (2014) A20 controls intestinal homeostasis through cell-specific activities. Nat Commun 5:5103 |
| abstractText | The transcription factor NF-kappaB is indispensable for intestinal immune homeostasis, but contributes to chronic inflammation and inflammatory bowel disease (IBD). A20, an inhibitor of both NF-kappaB 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. |
