Reviews and PerspectivesReviews in Basic and Clinical Gastroenterology and HepatologyInflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair
Section snippets
Intercellular Junctions
The intestinal epithelium is dynamically renewed within a week. It is truly remarkable that barrier properties are not only maintained but modified as crypt-progenitor stem cells proliferate, differentiate, and are shed at the luminal surface (Figure 1A).10 Intestinal epithelial stem cells generate multiple cell lineages, including absorptive enterocytes (80% of the cells), mucus-producing goblet cells, enteroendocrine cells, and antimicrobial peptide-producing Paneth cells. Microfold cells are
Effects of Inflammation
Mucosal inflammatory diseases are typically associated with compromised epithelial barrier function. It is generally believed that the trafficking of immune cells in concert with the release of different mediators represent key mechanisms of barrier disruption in the inflamed intestinal mucosa. Furthermore, it is increasingly appreciated that the luminal microflora promotes mucosal inflammatory responses, especially under conditions of altered epithelial permeability (recently reviewed in
Inflammation and Restoration of Mucosal Barrier Function
Although the deleterious effects of neutrophils on tissue homeostasis are commonly emphasized, the arrival of neutrophils and monocytes to sites of inflammation initiates anti-inflammatory signals that promote resolution. Specifically, leukocytes and epithelial cells promote resolution of inflammation by releasing factors such as annexin 1, resolvins, lipoxins, maresins, and protectins. These are released in a spatiotemporal manner and signal via G-protein−coupled receptors to coordinate
Conclusions
The intestinal epithelial barrier is at the interface between luminal microbes and the mucosal immune system and, therefore, helps maintain mucosal homeostasis. This barrier is not only determined by complex interactions between many TJ proteins, but is also regulated by proteins within other intercellular junction complexes. Precise regulation of barrier function and efficient repair after injury are essential for preventing pathologic inflammation. During mucosal inflammation, recruited
Acknowledgments
The authors thank Timothy L. Denning (Georgia State University) for helpful comments and Robin Kunkel (University of Michigan) for assistance in figure preparation. The authors also acknowledge the many significant contributions made by other investigators over the years who were not able to be referenced because of space and length restrictions.
Charles A. Parkos and Asma Nusrat contributed equally to this work.
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This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e16. Learning Objective: Upon completion of this activity, successful learners will be able to: (1) Distinguish general features of the intestinal epithelial barrier under both normal and inflammatory conditions. (2) Describe the general concepts of leukocyte transepithelial migration and mucosal barrier remodeling that occur during pathologic intestinal inflammation as observed in inflammatory bowel disease (IBD).
Conflicts of interest The authors disclose no conflicts.
Funding Research programs in the authors laboratories are supported by the NIH (DK072564, DK061379, DK079392 to Charles A. Parkos and DK055679,DK059888 to Asma Nusrat) and Department of Defense PR121194.
Author names in bold designate shared co-first authorship.