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Understanding the Epithelial Barrier in IBD

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Crohn's Disease and Ulcerative Colitis

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Abstract

The intestinal epithelial barrier is critical for maintaining a balance between potentially noxious luminal contents of the gut and the mucosal immune system. Defects in barrier function are associated with both Crohn’s disease and ulcerative colitis, and are also present in some healthy first-degree relatives. Impaired barrier function is associated with increased risk of Crohn’s disease relapse of patients in clinical remission. The tight junction, which seals the space between adjacent epithelial cells, is the primary determinant of permeability in the absence of epithelial injury, e.g. ulceration. The tight junction is formed by a complex of occludin, claudins, ZO-1, and the actomyosin cytoskeleton; the interactions between components are dynamically regulated to modify paracellular flux. The functional properties of the tight junction can be modified in response to either physiological stimuli of cytokines, e.g. TNF, IFNγ, and IL-13. Under pathological conditions, increased paracellular permeability may allow luminal material to access the lamina propria, thereby enhancing immune activation and triggering a recurrent cycle of barrier dysfunction and inflammation. Tight junction dysregulation may thereby play a central role in inflammatory bowel disease by linking mucosal immune responses to barrier function. As such, the potential of the tight junction as a target for therapeutic intervention should be considered.

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Authors and Affiliations

  1. Department of Pathology, The University of Chicago, 5841 South Maryland, MC 1089, Chicago, IL, 60637, USA

    Matthew A. Odenwald Ph.D. & Jerrold R. Turner M.D., Ph.D.

  2. Departments of Pathology and Medicine (GI), Brigham and Women’s Hospital and Harvard Medical School, 20 Shattuck St., TH1428, Boston, MA, 02116, USA

    Jerrold R. Turner M.D., Ph.D.

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Correspondence to Jerrold R. Turner M.D., Ph.D. .

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  1. Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Charité Medical School—Humboldt-University of Berlin, Berlin, Germany

    Daniel C. Baumgart

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Odenwald, M.A., Turner, J.R. (2017). Understanding the Epithelial Barrier in IBD. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Cham. https://doi.org/10.1007/978-3-319-33703-6_3

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