Induced somatic inactivation of STAT3 in mice triggers the development of a fulminant form of enterocolitis

Tonino Alonzi*, Ian P. Newton, Paul J. Bryce, Emma Di Carlo, Giuseppe Lattanzio, Marco Tripodi, Piero Musiani, Valeria Poli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

We have generated mice in which the gene encoding the transcription factor STAT3 can be inactivated in multiple cell types by triggering the endogenous production of type I interferon. Gene inactivation is particularly effective in the liver and the adipose tissue, as well as in macrophages and gut epithelial cells. Upon induction of the mutation, mice develop a wasting syndrome culminating in an aggressive and fatal form of enterocolitis, limited to the large intestine, within 2-3 weeks after the treatment. The disease is characterised by massive infiltration of the gut mucosa by macrophages, granulocytes and CD4+ cells, increased expression of endothelial adhesion molecules and high production of the cytokines interleukin (IL)-6, IL-12, interferon-γ and IL-10. IL-12 p40 plays a pivotal role in disease development as in vivo treatment with neutralising antibodies completely prevents its onset. Interestingly, oral treatment with wide spectrum antibiotics does not have any effect on either the onset or the development of colitis. Taken together, these data show that STAT3 plays a crucial role in the maintenance of intestinal homeostasis and possibly in mediating specialised cell functions in the intestinal epithelium.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalCytokine
Volume26
Issue number2
DOIs
StatePublished - Apr 21 2004

Keywords

  • Conditional gene inactivation
  • Enterocolitis
  • Inflammation
  • Inflammatory bowel disease
  • STAT3

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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