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World J Gastroenterol. Jul 21, 2011; 17(27): 3198-3203
Published online Jul 21, 2011. doi: 10.3748/wjg.v17.i27.3198
From intestinal stem cells to inflammatory bowel diseases
Michael Gersemann, Eduard Friedrich Stange, Jan Wehkamp
Michael Gersemann, Eduard Friedrich Stange, Jan Wehkamp, Internal Medicine I, Robert Bosch Hospital, Auerbachstrasse 110, D-70376 Stuttgart, Germany
Michael Gersemann, Eduard Friedrich Stange, Jan Wehkamp, Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology and University of Tübingen, Auerbachstrasse 112, D-70376 Stuttgart, Germany
Author contributions: Gersemann M, Stange EF and Wehkamp J have been researching the pathogenesis of Crohn’s disease and ulcerative colitis for many years. This review article was a joint work.
Supported by The Robert Bosch Foundation, Stuttgart, Germany and the Emmy Noether program (Wehkamp J) of the Deutsche Forschungsgemeinschaft (DFG)
Correspondence to: Michael Gersemann, MD, Internal Medicine I, Robert Bosch Hospital, Auerbachstrasse 110, D-70376 Stuttgart, Germany. michael.gersemann@rbk.de
Telephone: +49-711-81015912 Fax: +49-711-81013793
Received: December 10, 2010
Revised: February 9, 2011
Accepted: February 16, 2011
Published online: July 21, 2011
Abstract

The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn’s disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in developing IBD is beyond debate. In the last few years, the focus has changed from adaptive towards innate immunity. Crohn’s ileitis is associated with a deficiency of the antimicrobial shield, as shown by a reduced expression and secretion of the Paneth cell defensin HD5 and HD6, which is related to a Paneth cell differentiation defect mediated by a diminished expression of the Wnt transcription factor TCF4. In UC, the protective mucus layer, acting as a physical and chemical barrier between the gut epithelium and the luminal microbes, is thinner and in part denuded as compared to controls. This could be caused by a missing induction of the goblet cell differentiation factors Hath1 and KLF4 leading to immature goblet cells. This defective Paneth and goblet cell differentiation in Crohn’s ileitis and UC may enable the luminal microbes to invade the mucosa and trigger the inflammation. The exact molecular mechanisms behind ileal CD and also UC must be further clarified, but these observations could give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.

Keywords: Inflammatory bowel disease; Paneth cells; Goblet cells; Cell differentiation; TCF4; Hath1; KLF4