Inflammatory bowel disease: an impaired barrier disease
- Simon JägerAffiliated withDepartment of Internal Medicine I, Robert Bosch Hospital
- , Eduard F. StangeAffiliated withDepartment of Internal Medicine I, Robert Bosch Hospital
- , Jan WehkampAffiliated withDepartment of Internal Medicine I, Robert Bosch HospitalDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Email author
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
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.
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.
KeywordsPaneth cell Defensin Inflammatory bowel disease Innate immunity Crohn’s disease pathogenesis
- Inflammatory bowel disease: an impaired barrier disease
Langenbeck's Archives of Surgery
Volume 398, Issue 1 , pp 1-12
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Paneth cell
- Inflammatory bowel disease
- Innate immunity
- Crohn’s disease pathogenesis
- Industry Sectors