STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing
Open accessAbstract
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. STAT3(IEC-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.
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Intestinal epithelium-specific STAT3 knockout impairs epithelial wound healing.
“Impaired epithelial wound healing”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Pickert et al., 2009
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- Authors
- Pickert, G., Neufert, C., Leppkes, M., Zheng, Y., Wittkopf, N., Warntjen, M., Lehr, H.-A., Hirth, S., Weigmann, B., Wirtz, S., Ouyang, W., Neurath, M. F., & Becker, C.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Genentech (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Universitätsklinikum Erlangen (DE)
- Corresponding author
- Becker, Christoph
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-06-29
- Volume
- 206
- Issue
- 7
- Pages
- 1465-1472
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2715097
- OpenAlex
- W2169355315
- Cited by
- 1,043
- References
- 3
- Citations by year
- 2026: 59 · 2025: 42 · 2024: 62 · 2023: 68 · 2022: 49 · 2021: 61 · 2020: 62 · 2019: 71 · 2018: 71 · 2017: 63 · 2016: 62 · 2015: 65 · 2014: 72 · 2013: 86 · 2012: 59
- FWCI
- 24.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- Pfizer
- Deutsche Forschungsgemeinschaft (SFB548)
- Genentech
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- STAT3, IL-22 signaling, intestinal epithelial cells, mucosal wound healing, colitis, DSS-induced colitis, epithelial restitution, Toll-like receptors, CD11c+ cells, intestinal homeostasis, apoptosis, cellular stress response, conditional knockout mice
- MeSH terms
- Interleukin-22, Animals, Colitis, Epithelial Cells, Inflammation, Interleukins, Intestinal Mucosa, Mice, Inbred C57BL, Wound Healing, Signal Transduction, Interleukin-6, Dextran Sulfate, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, STAT3 Transcription Factor, Mice
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