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Although the critical factors necessary for IBD pathogenesis remain mysterious, interest in the potential role of defective epithelial barrier function continues to grow. New insight into the mechanisms responsible for barrier dysfunction in IBD may lead to understanding its contribution to disease development and progression.
Ulcerative colitis and Crohn’s disease, collectively known as inflammatory bowel disease (IBD), are major causes of lifetime morbidity. Although these diseases are often differentiated clinically on the basis of disease distribution and morphology, they share many characteristics. Each disease clearly involves an abnormal mucosal inflammatory response, and data from various sources suggest that luminal stimuli and epithelial cell dysfunction can also contribute to disease pathogenesis or progression. Defective epithelial barrier function, which can be measured as increased intestinal permeability, has been implicated in IBD1 and can predict relapse during clinical remission.2,3 Increased permeability is also present in a subset of unaffected first-degree relatives of patients with Crohn’s disease.4,5 As a result of these observations, the mechanisms of barrier function and permeability defects are thought to have a great potential in defining IBD pathogenesis and guiding the development of novel treatments.
The mucosal barrier is established by the single layer of epithelial cells that line the intestine, with erosion and ulcerations being obvious sources of focal barrier defects. The tight junction seals the space between adjacent epithelial cells and, in intact gastrointestinal epithelia, tight junction permeability is the rate-limiting step that defines the overall epithelial permeability. Thus, tight junction defects may be an important source of the overall intestinal barrier defects—that is, permeability increases—seen in patients with IBD. In this issue of Gut, Zeissig et al6 (see page 61) provide strong evidence that the tight junction barrier function is altered in IBD, and also suggest some specific mechanisms that …