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Mucosal Immunol. 2017 Sep;10(5):1211-1223. doi: 10.1038/mi.2016.125. Epub 2017 Jan 18.

c-Jun N-terminal kinase 2 promotes enterocyte survival and goblet cell differentiation in the inflamed intestine.

Author information

1
Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
2
Department of Microbiology, University Hospital RWTH Aachen, Aachen, Germany.
3
Howard Hughes Medical Institute and University of Massachusetts Medical School, Worcester, Massachusetts, USA.
4
Interdisciplinary Center for Clinical Research (IZKF), University Hospital RWTH Aachen, Aachen, Germany.
5
Institute of Pathology, Klinikum Braunschweig, Braunschweig, Germany.
6
GeneXplain GmbH, Wolfenbüttel, Germany.

Abstract

c-Jun N-terminal kinases (JNKs) contribute to immune signaling but their functional role during intestinal mucosal inflammation has remained ill defined. Using genetic mouse models, we characterized the role of JNK1 and JNK2 during homeostasis and acute colitis. Epithelial apoptosis, regeneration, differentiation, and barrier function were analyzed in intestinal epithelium-specific (ΔIEC) or complete JNK1 and bone marrow chimeric or complete JNK2 deficient mice as well as double-knockout animals (JNK1ΔIECJNK2-/-) during homeostasis and acute dextran sulfate sodium (DSS)-induced colitis. Results were confirmed using human HT-29 cells and wild-type or JNK2-deficient mouse intestinal organoid cultures. We show that nonhematopoietic JNK2 but not JNK1 expression confers protection from DSS-induced intestinal inflammation reducing epithelial barrier dysfunction and enterocyte apoptosis. JNK2 additionally enhanced Atonal homolog 1 expression, goblet cell and enteroendocrine cell differentiation, and mucus production under inflammatory conditions. Our results identify a protective role of epithelial JNK2 signaling to maintain mucosal barrier function, epithelial cell integrity, and mucus layer production in the event of inflammatory tissue damage.

PMID:
28098247
DOI:
10.1038/mi.2016.125
[Indexed for MEDLINE]

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