Internal Medicine I, Robert Bosch Hospital, Auerbachstrasse 110, D-70376 Stuttgart, Germany.
World J Gastroenterol. 2011 Jul 21;17(27):3198-203. doi: 10.3748/wjg.v17.i27.3198.
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.
炎症性肠病（IBD）的两种实体，即克罗恩病（CD）和溃疡性结肠炎（UC）的发病机制仍然很复杂，仍在研究中。微生物菌群在发展 IBD 中的重要性是毋庸置疑的。在过去的几年中，人们的研究重点已经从适应性免疫转向了先天免疫。正如潘氏细胞防御素 HD5 和 HD6 的表达和分泌减少所表明的那样，克罗恩病回肠炎与抗菌屏障的缺陷有关，这与 Wnt 转录因子 TCF4 的表达减少介导的潘氏细胞分化缺陷有关。在 UC 中，保护性黏液层作为肠上皮细胞和腔微生物之间的物理和化学屏障，比对照组更薄，部分裸露。这可能是由于缺乏对杯状细胞分化因子 Hath1 和 KLF4 的诱导，导致不成熟的杯状细胞。这种在回肠 CD 和 UC 中潘氏细胞和杯状细胞分化的缺陷可能使腔微生物能够侵入粘膜并引发炎症。回肠 CD 背后的确切分子机制以及 UC 必须进一步阐明，但这些观察结果可能会引发新的治疗策略，基于对保护性先天免疫系统的刺激。
