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World J Gastroenterol. Sep 28, 2008; 14(36): 5499-5503
Published online Sep 28, 2008. doi: 10.3748/WJG.14.5499
Crohn’s disease-Defect in innate defence
Michael Gersemann, Jan Wehkamp, Klaus Fellermann, Eduard Friedrich Stange
Michael Gersemann, Jan Wehkamp, Klaus Fellermann, Eduard Friedrich Stange, Robert Bosch Hospital and Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany
Author contributions: Gersemann M, Wehkamp J, Fellermann K, and Stange EF are working on the pathogenesis of both intestinal bowel diseases, Crohn’s disease and ulcerative colitis since many years resulting in a couple of original works. This review article was a joint work.
Supported by The Robert Bosch Foundation, Stuttgart, Germany and the Emmy Noether program (J.W.) of the Deutsche Forschungsgemeinschaft (DFG)
Correspondence to: Eduard Friedrich Stange, MD, Robert Bosch Hospital, Internal Medicine I Auerbachstr. 110, D-70376 Stuttgart, Germany. eduard.stange@rbk.de
Telephone: +49-711-81013406 Fax: +49-711-81013793
Received: July 30, 2008
Revised: August 5, 2008
Accepted: August 12, 2008
Published online: September 28, 2008
Abstract

Crohn’s disease may prinicipally involve the whole gastrointestinal tract. Most commonly, the inflammation occurs in the small intestine and/or in the colon with stable disease location over the years. The pathogenesis of both disease phenotypes is complex, the likely primary defect lies in the innate rather than adaptive immunity, particularly in the chemical antimicrobial barrier of the mucosa. Crohn’s ileitis is associated with a reduced expression of the Wnt signalling pathway transcription factor T-cell factor 4 (TCF4), which is regulating Paneth cell differentiation. As a result, the alpha-defensins and principal Paneth cell products HD5 and HD6 are deficiently expressed in ileal disease, independent of current inflammation. In contrast, Crohn’s colitis is typically associated with an impaired induction of the beta-defensins HBD2 and HBD3 caused by fewer gene copy numbers in the gene locus of the beta-defensins on chromosome 8. This ileal and colonic defect in innate defence mediated by a deficiency of the protective alpha- and beta-defensins may enable the luminal microbes to invade the mucosa and trigger the inflammation. A better understanding of the exact molecular mechanisms behind ileal and colonic Crohn’s disease may give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.

Keywords: Crohn’s disease, Intestinal stem cell, Differentiation, Defensins, Transcription factor T-cell factor 4