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| 1 | From intestinal stem cells to inflammatory bowel diseases显示文摘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 thin- ner 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 enablethe 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. | Michael Gersemann Eduard Friedrich Stange Jan Wehkamp | 2011 | World Journal of Gastroenterology2011，17，27： | 19 |
| 2 | Crohn’s disease-Defect in innate defence显示文摘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. | Michael Gersemann Jan Wehkamp Klaus Fellermann Eduard Friedrich Stange | 2008 | World Journal of Gastroenterology2008，14，36： | 7 |
| 3 | Innate immune dysfunction in inflammatory bowel disease显示文摘 | Gersemann M Wehkamp J Stange EF | 2012 | J Intern Med2012，271，5： | 1 |
| 4 | Differences in goblet cell differentiation between Crohn’s disease and ulcerative colitis显示文摘 | Michael Gersemann Svetlana Becker Irmgard Kübler Maureen Koslowski Guoxing Wang Klaus Robert Herrlinger Joscha Griger Peter Fritz Klaus Fellermann Matthias Schwab Jan Wehkamp Eduard Friedrich Stange | 2008 | Differentiation2008，，1： | 1 |
| 5 | Crohn′s disease--defect in innate defence显示文摘 | Gersemann M Wehkamp J Fellermann K | 2008 | World J Gastroenterol2008，14，： | 1 |
| 6 | Human colonic mucus is a reservoir for antimicrobial peptides显示文摘 | Lena Antoni Sabine Nuding Dagmar Weller Michael Gersemann German Ott Jan Wehkamp Eduard F. Stange | 2013 | Journal of Crohn’s and Colitis2013，，： | 1 |
| 7 | Differences in gob- let cell differentiation between Crohn's disease and ulcerative colitis显示文摘 | Gersemann M Becker S Kubler I | 2009 | Differentiation2009，77，1： | 1 |
| 8 | Differences in goblet cell differentiation between Crohn' s disease and ulcerative colitis 显示文摘 | Gersemann M Becker S Kubler I | 2009 | Differentiation2009，77，1： | 1 |
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