发炎性肠道疾病（inflammatory bowel disease, IBD）主要是指克隆氏症（Crohn's disease, CD）及溃疡性结肠炎（ulcerative colitis, UC）两种疾病，临床上的特点是容易复发，并形成慢性以及无法预期的病程。全世界约有四百万人受到这种疾病的影响。
研究人员希望可以发展出有效的疗法，但是必需要先了解这种疾病底下的分子机制。德国科隆和美因法大学和位于意大利的欧洲分子生物学实验室的小鼠生物学单位(EMBL)的研究人员，解开了引起慢性发炎性肠道疾病的分子信号。这项研究发表于这一期的Nature网络版中。研究结果证实，阻拦这种信号分子会造成小鼠严重的肠道发炎，这可能是人类发炎性肠道疾病的分子机制。
研究人员调查NF kb如何帮助肠道上皮细胞应付压力。他们利用遗传技术，产生不表现NEMO 的一个小鼠模型，这种蛋白质对于活化小肠上皮细胞NF kb是非常重要的。结果，这些小鼠发生与人类发炎性肠道疾病非常相似的慢性肠道炎症。因此研究人员认为，肠道上皮的NF kb信号途径发生缺陷，可能是导致发炎性肠道疾病的原因。
(资料来源 : Bio.com)
部分英文原文：
Nature advance online publication 14 March 2007 | doi:10.1038/nature05698; Received 8 December 2006; Accepted 23 February 2007; Published online 14 March 2007
Epithelial NEMO links innate immunity to chronic intestinal inflammation
Arianna Nenci1,2,6, Christoph Becker3,6, Andy Wullaert1, Ralph Gareus1, Geert van Loo2, Silvio Danese4, Marion Huth2, Alexei Nikolaev3, Clemens Neufert3, Blair Madison5, Deborah Gumucio5, Markus F. Neurath3,6 and Manolis Pasparakis1,2
Institute for Genetics, University of Cologne, Zülpicher Strasse 47, 50674 Cologne, Germany
EMBL Mouse Biology Unit, I-00016 Monterotondo, Italy
Laboratory of Clinical Immunology, I. Department of Medicine, University of Mainz, Obere Zahlbacher Strasse 63, 55131 Mainz, Germany
Division of Gastroenterology, Istituto Clinico Humanitas-IRCCS in Gastroenterology, Viale Manzoni 56, 20089 Rozzano, Milan, Italy
Department of Cell & Developmental Biology, Center for Organogenesis, The University of Michigan, Ann Arbor, Michigan 48109-0616, USA
These authors contributed equally to this work.
Correspondence to: Manolis Pasparakis1,2 Correspondence and requests for materials should be addressed to M.P. (Email: pasparakis@uni-koeln.de).
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Deregulation of intestinal immune responses seems to have a principal function in the pathogenesis of inflammatory bowel disease1, 2, 3, 4. The gut epithelium is critically involved in the maintenance of intestinal immune homeostasis—acting as a physical barrier separating luminal bacteria and immune cells, and also expressing antimicrobial peptides3, 5, 6. However, the molecular mechanisms that control this function of gut epithelial cells are poorly understood. Here we show that the transcription factor NF-B, a master regulator of pro-inflammatory responses7, 8, functions in gut epithelial cells to control epithelial integrity and the interaction between the mucosal immune system and gut microflora. Intestinal epithelial-cell-specific inhibition of NF-B through conditional ablation of NEMO (also called IB kinase- (IKK)) or both IKK1 (IKK) and IKK2 (IKK)—IKK subunits essential for NF-B activation7, 8, 9—spontaneously caused severe chronic intestinal inflammation in mice. NF-B deficiency led to apoptosis of colonic epithelial cells, impaired expression of antimicrobial peptides and translocation of bacteria into the mucosa. Concurrently, this epithelial defect triggered a chronic inflammatory response in the colon, initially dominated by innate immune cells but later also involving T lymphocytes. Deficiency of the gene encoding the adaptor protein MyD88 prevented the development of intestinal inflammation, demonstrating that Toll-like receptor activation by intestinal bacteria is essential for disease pathogenesis in this mouse model. Furthermore, NEMO deficiency sensitized epithelial cells to tumour-necrosis factor (TNF)-induced apoptosis, whereas TNF receptor-1 inactivation inhibited intestinal inflammation, demonstrating that TNF receptor-1 signalling is crucial for disease induction. These findings demonstrate that a primary NF-B signalling defect in intestinal epithelial cells disrupts immune homeostasis in the gastrointestinal tract, causing an inflammatory-bowel-disease-like phenotype. Our results identify NF-B signalling in the gut epithelium as a critical regulator of epithelial integrity and intestinal immune homeostasis, and have important implications for understanding the mechanisms controlling the pathogenesis of human inflammatory bowel disease.
