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A20 controls intestinal homeostasis through cell-specific activities

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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
The transcription factor NF-kappa B is indispensable for intestinal immune homeostasis, but contributes to chronic inflammation and inflammatory bowel disease (IBD). A20, an inhibitor of both NF-kappa B 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.
Keywords
GENE ATG16L1, COLORECTAL-CANCER, CROHNS-DISEASE, PANETH CELLS, INFLAMMATORY-BOWEL-DISEASE, ULCERATIVE-COLITIS, INNATE IMMUNITY, GUT MICROBIOME, RHEUMATOID-ARTHRITIS, STEM-CELL

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Citation

Please use this url to cite or link to this publication:

MLA
Vereecke, Lars, Sara Vieira-Silva, Thomas Billiet, et al. “A20 Controls Intestinal Homeostasis Through Cell-specific Activities.” NATURE COMMUNICATIONS 5 (2014): n. pag. Print.
APA
Vereecke, L., Vieira-Silva, S., Billiet, T., van Es, J. H., Mc Guire, C., Slowicka, K., Sze, M., et al. (2014). A20 controls intestinal homeostasis through cell-specific activities. NATURE COMMUNICATIONS, 5.
Chicago author-date
Vereecke, Lars, Sara Vieira-Silva, Thomas Billiet, Johan H van Es, Conor Mc Guire, Karolina Slowicka, Mozes Sze, et al. 2014. “A20 Controls Intestinal Homeostasis Through Cell-specific Activities.” Nature Communications 5.
Chicago author-date (all authors)
Vereecke, Lars, 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. 2014. “A20 Controls Intestinal Homeostasis Through Cell-specific Activities.” Nature Communications 5.
Vancouver
1.
Vereecke L, Vieira-Silva S, Billiet T, van Es JH, Mc Guire C, Slowicka K, et al. A20 controls intestinal homeostasis through cell-specific activities. NATURE COMMUNICATIONS. 2014;5.
IEEE
[1]
L. Vereecke et al., “A20 controls intestinal homeostasis through cell-specific activities,” NATURE COMMUNICATIONS, vol. 5, 2014.
@article{5752994,
  abstract     = {The transcription factor NF-kappa B is indispensable for intestinal immune homeostasis, but contributes to chronic inflammation and inflammatory bowel disease (IBD). A20, an inhibitor of both NF-kappa B 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.},
  articleno    = {5103},
  author       = {Vereecke, Lars and Vieira-Silva, Sara and Billiet, Thomas and van Es, Johan H and Mc Guire, Conor and Slowicka, Karolina and Sze, Mozes and van den Born, Maaike and De Hertogh, Gert and Clevers, Hans and Raes, Jeroen and Rutgeerts, Paul and Vermeire, Severine and Beyaert, Rudi and van Loo, Geert},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {GENE ATG16L1,COLORECTAL-CANCER,CROHNS-DISEASE,PANETH CELLS,INFLAMMATORY-BOWEL-DISEASE,ULCERATIVE-COLITIS,INNATE IMMUNITY,GUT MICROBIOME,RHEUMATOID-ARTHRITIS,STEM-CELL},
  language     = {eng},
  pages        = {12},
  title        = {A20 controls intestinal homeostasis through cell-specific activities},
  url          = {http://dx.doi.org/10.1038/ncomms6103},
  volume       = {5},
  year         = {2014},
}

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