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Understanding the Epithelial Barrier in Inflammatory Bowel Disease

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Crohn's Disease and Ulcerative Colitis

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Abstract

Appropriate function of 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 actin cytoskeleton; the interactions between components are dynamically regulated to modify paracellular flux. The functional properties of the tight junction are regulated both by physiological stimuli and by cytokines, e.g., TNF, IFNγ (gamma), and IL-13. Under pathological conditions, increased paracellular permeability in response to cytokine production may allow luminal material to access the lamina propria, further activating immune responses and continuing the cycle of barrier dysfunction and inflammation. This model predicts that the tight junction may play a central role in inflammatory bowel disease by balancing the mucosal immune response with the luminal microbiota. As such, the potential of the tight junction as a target for therapeutic intervention should be considered.

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Acknowledgments

Work in the authors’ laboratory is supported by U.S. National Institutes of Health (R01DK61931, R01DK68271, P01DK67887, and F32DK091017), the University of Chicago Digestive Disease Research Core Center (NIH P30DK42086), the University of Chicago Cancer Center (P30CA14599), the University of Chicago Institute for Translational Medicine (NIH UL1RR024999), the U.S. Department of Defense (W81XWH-09-1-0341), the Broad Medical Research Foundation, and the Crohn’s and Colitis Foundation of America.

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Authors and Affiliations

  1. Department of Pathology, University of Chicago, 5841 S. Maryland Avenue, MC 1089 AMB P-526, Chicago, IL, 60637, USA

    Emily M. Bradford PhD, Emily S. Turner & Jerrold R. Turner MD, PhD

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  1. Emily M. Bradford PhD
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  2. Emily S. Turner
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  3. Jerrold R. Turner MD, PhD
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Correspondence to Jerrold R. Turner MD, PhD .

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  1. Medical School of the Humboldt Universit, Department of Medicine, Charité Medical Center, Virchow Hospita, Berlin, 13344, Germany

    Daniel C. Baumgart

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Bradford, E.M., Turner, E.S., Turner, J.R. (2012). Understanding the Epithelial Barrier in Inflammatory Bowel Disease. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0998-4_4

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  • DOI: https://doi.org/10.1007/978-1-4614-0998-4_4

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