title: From intestinal stem cells to inflammatory bowel diseases.
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.
authors.affiliation: Internal Medicine I, Robert Bosch Hospital, Auerbachstrasse 110, D-70376 Stuttgart, Germany. michael.gersemann@rbk.de
authors.forename: Michael
authors.initials: M
authors.lastname: Gersemann
authors.forename: Eduard Friedrich
authors.initials: EF
authors.lastname: Stange
authors.forename: Jan
authors.initials: J
authors.lastname: Wehkamp
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D003093:Colitis, Ulcerative / Q000175:diagnosis; D003424:Crohn Disease / Q000175:diagnosis; D020397:Goblet Cells / Q000166:cytology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D019879:Paneth Cells / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism; D023084:alpha-Defensins / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D000073940:Transcription Factor 4; D014157:Transcription Factors; D023084:alpha-Defensins; C500942:ATOH1 protein, human; C000715467:KLF4 protein, human; C532096:TCF4 protein, human