The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20082683
The Journal of Experimental Medicine, Vol. 206, No. 7, 1465-1472
The Rockefeller University Press, 0022-1007 $30.00
© Pickert et al.
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BRIEF DEFINITIVE REPORT

 STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing

Geethanjali Pickert1, Clemens Neufert2, Moritz Leppkes1, Yan Zheng4, Nadine Wittkopf1, Moritz Warntjen1, Hans-Anton Lehr3, Sebastian Hirth1, Benno Weigmann1, Stefan Wirtz1, Wenjun Ouyang4, Markus F. Neurath5, and Christoph Becker1

1 Institute of Molecular Medicine and 2 I. Department of Medicine, Johannes Gutenberg University of Mainz, 55131 Mainz, Germany
3 Institut Universitaire de Pathologie, Centre Hospitalier, Universitaire Vaudois, 1011 Lausanne, Switzerland
4 Department of Immunology, Genentech, South San Francisco, CA 94080
5 Department of Medicine 1, University Hospital Erlangen, 91054 Erlangen, Germany

CORRESPONDENCE Christoph Becker: chbecker{at}uni-mainz.de

Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3IEC-KO mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22–dependent mucosal wound healing.

G. Pickert and C. Neufert contributed equally to this paper.

Abbreviations used: DSS, dextran sodium sulfate; IBD, inflammatory bowel disease; IEC, intestinal epithelial cell; LPMC, lamina propria mononuclear cell; pSTAT3, phosphorylated STAT3; TLR, Toll-like receptor; TUNEL, Tdt-mediated dUTP-biotin nick-end labeling.

© 2009 Pickert et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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