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A New Look at Crohn's Disease

Published on Aug 1, 2006in Annals of the New York Academy of Sciences4.29
· DOI :10.1196/annals.1326.030
Jan Wehkamp42
Estimated H-index: 42
(Robert Bosch Hospital),
Eduard F. Stange56
Estimated H-index: 56
(Robert Bosch Hospital)
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Abstract
: Crohn's disease (CD), a chronic inflammatory disease of the intestinal mucosa is usually located in the small intestine (ileum) and or in the colon. Ileal CD has been linked to a mutation in the NOD2 gene, a bacterial recognition protein. A disturbed antimicrobial defense as provided by an arsenal of different epithelial defensins seems to be a critical factor in disease pathogenesis. Defensins are antimicrobial peptides and in the ileum are mainly expressed in Paneth cells (PCs), epithelial cells that also express NOD2. In the colon, defensins are expressed by enterocytes or metaplastic PCs. Ileal CD patients are characterized by a reduced antibacterial activity and a specific reduction of ileal PC defensins. In ileal Crohn's patients displaying a NOD2 mutation, this decrease is even more pronounced. In contrast, CD of the colon is characterized by an impaired induction of beta defensins in enterocytes. In conclusion, the regional localizations of CD, either ileal or colonic disease, can be linked to different defects in defensin expression. In line with these new findings, we predict that future therapeutic strategies aimed at restoring the host–microbe balance at the intestinal mucosa may prove superior to those that broadly suppress inflammation and adaptive immunity.
  • References (42)
  • Citations (54)
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References42
Newest
#1Jan Wehkamp (UC Davis: University of California, Davis)H-Index: 42
#2Nita H. Salzman (MCW: Medical College of Wisconsin)H-Index: 31
Last.Charles L. BevinsH-Index: 58
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#1Jan Wehkamp (UC Davis: University of California, Davis)H-Index: 42
#2Michael Schmid (Robert Bosch Hospital)H-Index: 1
Last.Eduard F. Stange (Robert Bosch Hospital)H-Index: 56
view all 4 authors...
#1Koichi S. Kobayashi (Harvard University)H-Index: 39
#2Mathias Chamaillard (UM: University of Michigan)H-Index: 34
Last.R. A. Flavell (Yale University)H-Index: 205
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Cited By54
Newest
#1Xiaolei Pei (PKU: Peking University)H-Index: 3
#2Danfeng Zheng (PKU: Peking University)H-Index: 2
Last.Dalong Ma (PKU: Peking University)H-Index: 27
view all 10 authors...
#1Mani P Grover (Deakin University)H-Index: 3
#2Sara Ballouz (CSHL: Cold Spring Harbor Laboratory)H-Index: 9
Last.Merridee A. Wouters (Deakin University)H-Index: 23
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View next paperReduced Paneth cell α-defensins in ileal Crohn's disease