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Langenbeck's Archives of Surgery
Published in: Langenbeck's Archives of Surgery 1/2013

01-01-2013 | Review Article

Inflammatory bowel disease: an impaired barrier disease

Authors: Simon Jäger, Eduard F. Stange, Jan Wehkamp

Published in: Langenbeck's Archives of Surgery | Issue 1/2013

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Abstract

Background

The intestinal barrier is a delicate structure composed of a single layer of epithelial cells, the mucus, commensal bacteria, immune cells, and antibodies. Furthermore, a wealth of antimicrobial peptides (AMPs) can be found in the mucus and defend the mucosa. Different lines of investigations now point to a prominent pathophysiological role of defensins, an important family of AMPs, in the pathogenesis of inflammatory bowel disease and, particularly, in small intestinal Crohn’s disease.

Purpose

In this review, we introduce the different antimicrobial peptides of the intestinal mucosa and describe their function, their expression pattern along the gastrointestinal tract, and their spatial relationship to the mucus layer. We then focus on the alterations found in inflammatory bowel disease. Small intestinal Crohn’s disease (CD) is closely linked to defects in Paneth cells (specialized secretory epithelial cells at the bottom crypts) which secrete α-defensin human defensin (HD)-5 in huge quantities in healthy individuals. Decreased expression of these antimicrobial peptides is found in ileal CD, and single nucleotide polymorphisms with the highest linkage to CD affect genes involved in Paneth cell biology and defensin secretion. Additionally, antimicrobial peptides have a role in ulcerative colitis, where the depleted mucus layer cannot fulfill its crucial function of binding defensins and other AMPs to their proper site of action.

Conclusion

Inflammatory bowel disease arises when the mucosal barrier is compromised in its defense against challenges from the intestinal microbiota. In ileal CD, a strong association can be found between diminished expression or defective function of defensins and the advent of intestinal inflammation.
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Metadata
Title
Inflammatory bowel disease: an impaired barrier disease
Authors
Simon Jäger
Eduard F. Stange
Jan Wehkamp
Publication date
01-01-2013
Publisher
Springer-Verlag
Published in
Langenbeck's Archives of Surgery / Issue 1/2013
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI
https://doi.org/10.1007/s00423-012-1030-9

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