Cited by 1,775Gastrointestinal motility and disordersBarrier Structure and Function StudiesInflammatory Bowel Disease

Intestinal barrier function: molecular regulation and disease pathogenesis

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Groschwitz, Katherine R., Hogan, Simon P.·2009·Journal of Allergy and Clinical Immunology

Abstract

The intestinal epithelium is a single-cell layer that constitutes the largest and most important barrier against the external environment. It acts as a selectively permeable barrier, permitting the absorption of nutrients, electrolytes, and water while maintaining an effective defense against intraluminal toxins, antigens, and enteric flora. The epithelium maintains its selective barrier function through the formation of complex protein-protein networks that mechanically link adjacent cells and seal the intercellular space. The protein networks connecting epithelial cells form 3 adhesive complexes: desmosomes, adherens junctions, and tight junctions. These complexes consist of transmembrane proteins that interact extracellularly with adjacent cells and intracellularly with adaptor proteins that link to the cytoskeleton. Over the past decade, there has been increasing recognition of an association between disrupted intestinal barrier function and the development of autoimmune and inflammatory diseases. In this review we summarize the evolving understanding of the molecular composition and regulation of intestinal barrier function. We discuss the interactions between innate and adaptive immunity and intestinal epithelial barrier function, as well as the effect of exogenous factors on intestinal barrier function. Finally, we summarize clinical and experimental evidence demonstrating intestinal epithelial barrier dysfunction as a major factor contributing to the predisposition to inflammatory diseases, including food allergy, inflammatory bowel diseases, and celiac disease.

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Crossref · 10.1016/j.jaci.2009.05.038

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  • Enterocytes connect with each other in a continuous epithelial cell layer via adhesive junctional proteins that make up tight junction proteins, adherens junction proteins, gap junction proteins, and desmosomes.

    “Enterocytes connect with each other in a continuous epithelial cell layer via adhesive junctional proteins that make up tight junction (TJ) proteins, adherens junction (AJ) proteins, gap junction proteins, and desmosomes (Table 2).31,32”

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  1. [63]Harhaj NS Antonetti DA Regulation of tight junctions and loss of barrier function in pathophysiology Int J Biochem Cell Biol 2004 36 1206 37 15109567

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Authors
Groschwitz, K. R., & Hogan, S. P.
Affiliations
Cincinnati Children's Hospital Medical Center (US)
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2009-07
Volume
124
Issue
1
Pages
3-20
ISSN
0091-6749 (ISSN-L)
OpenAlex
W1992152055
Cited by
1,775
References
266
Citations by year
2026: 123 · 2025: 152 · 2024: 181 · 2023: 145 · 2022: 143 · 2021: 179 · 2020: 145 · 2019: 126 · 2018: 115 · 2017: 88 · 2016: 73 · 2015: 63 · 2014: 63 · 2013: 49 · 2012: 44
FWCI
6.59
Type
journal article
Language
en
Open access
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of General Medical Sciences (T32GM063483)
  • National Institute of Allergy and Infectious Diseases (R01AI073553)
  • National Institute of Diabetes and Digestive and Kidney Diseases (F30 DK08211, F30DK082113)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
intestinal barrier function, intestinal epithelium, tight junctions, adherens junctions, desmosomes, cell adhesion complexes, cytoskeleton, innate immunity, adaptive immunity, autoimmune disease, inflammatory bowel disease, celiac disease, food allergy, barrier dysfunction, pathogenesis
MeSH terms
Humans, Intercellular Junctions, Intestinal Mucosa, Inflammatory Bowel Diseases

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