Tight junctions as targets and effectors of mucosal immune homeostasis
Open accessAbstract
Paracellular transport across the selectively permeable mucosal barrier is essential for health.Two distinct pathways, pore and leak, mediate transport across the tight junction, which is the rate-limiting step in paracellular flux.The permeabilities of these routes can be differentially regulated by immune and other stimuli and, conversely, have distinct effects on intestinal and systemic immune function.Defective epithelial barrier function is present in maladies including epidermal burn injury, environmental lung damage, renal tubular disease, and a range of immunemediated and infectious intestinal disorders.When the epithelial surface is intact, the paracellular pathway between cells is sealed by the tight junction.However, permeability of tight junctions varies widely across tissues and can be markedly impacted by disease.For example, tight junctions within the skin and urinary bladder are largely impermeant and their permeability is not regulated.In contrast, tight junctions of the proximal renal tubule and intestine are selectively permeable to water and solutes on the basis of their biophysical characteristics and, in the gut, can be regulated by the immune system with remarkable specificity.Conversely, modulation of tight junction barrier conductance, especially within the gastrointestinal tract, can impact immune homeostasis and diverse pathologies.Thus, tight junctions are both effectors and targets of immune regulation.Using the gastrointestinal tract as an example, this review explores current understanding of this complex interplay between tight junctions and immunity.
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The flux that occurs due to cell death (global barrier loss) is classified as the unrestricted pathway, in which there is no size limit of molecules or antigens that can cross the membrane.
“The flux that occurs due to cell death (global barrier loss) is classified as “unrestricted pathway,” in which there is no size limit of molecules or antigens that can cross the membrane.48”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [48]
Solutes and water cross tight junctions through 2 distinct pathways based on their size and charge selectivity: the pore pathway and the leak pathway.
“It was reported that solutes and water cross TJs through 2 distinct pathways based on their size and charge selectivity: the pore pathway48, 49, 50 and the leak pathway.48,51”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [48]
The mucosal immune system profoundly impacts gut barrier functions both in health and disease conditions.
“Additionally, the mucosal immune system profoundly impacts gut barrier functions both in health and disease conditions, reviewed previously.48,179, 180, 181, 182, 183”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [48]
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Regulation of Intestinal Barrier Function by Microbial Metabolites
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Gut barrier disruption and chronic disease
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Role of the endocannabinoid system in the regulation of intestinal homeostasis
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- Authors
- Zuo, L., Kuo, W.-T., & Turner, J. R.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Turner, Jerrold R.
- Venue
- Cellular and Molecular Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2020
- Volume
- 10
- Issue
- 2
- Pages
- 327-340
- ISSN
- 2352-345X (ISSN-L)
- PMC
- PMC7326733
- OpenAlex
- W3017272863
- Cited by
- 191
- References
- 134
- Citations by year
- 2026: 31 · 2025: 36 · 2024: 47 · 2023: 25 · 2022: 29 · 2021: 16 · 2020: 7
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cellular and Molecular Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (R01DK61931, R01DK68271, R24DK099803)
- Harvard Digestive Disease Center (P30DK034854)
- Department of Defense
- National Natural Science Foundation of China (81800464)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- tight junctions, mucosal immune homeostasis, paracellular permeability, epithelial barrier function, intestinal permeability, intestinal immunity
- MeSH terms
- Animals, Homeostasis, Humans, Intestinal Mucosa, Permeability, Immunity, Mucosal, Tight Junctions, Models, Animal, Mice
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