Increased epithelial uptake of protein antigens in the ileum of Crohn’s disease mediated by tumour necrosis factor α
Open accessAbstract
Background and aims: The exact nature of the epithelial barrier defect in Crohn’s disease remains to be elucidated. Previously we showed increased permeability to proteins in ileal Crohn’s disease. Our aims were to study if this barrier defect (a) involves endocytotic uptake of antigens and (b) is related to low grade inflammation not detectable by histology. Methods: Macroscopically normal segments of distal ileum of Crohn’s disease patients (n = 10) were subgrouped into non-inflamed (histologically unaffected) and slightly inflamed tissues and studied in Ussing chambers, with normal ileal specimens from colon cancer patients (n = 9) as controls. Endocytotic uptake into enterocytes of the protein antigen horseradish peroxidase was assessed by measuring the area of horseradish peroxidase containing endosomes in electron photomicrographs. Mucosal tumour necrosis factor α (TNF-α) mRNA was quantified using real time polymerase chain reaction. For comparison, the effects of low doses of TNF-α on endosomal uptake of horseradish peroxidase were studied in cultured T84 cells grown on filter supports. Results: The area of horseradish peroxidase containing endosomes was increased (p<0.001) in enterocytes of non-inflamed ileum of Crohn’s disease (2.8 (0.7) μm 2 /300 μm 2 ) compared with control ileum (0.6 (0.06)). In non-inflamed mucosa, a significant association between endosomal uptake and mucosal expression of TNF-α mRNA (p = 0.03) was found. Low concentrations of TNF-α (0.25–1.0 ng/ml) enhanced the endosomal uptake of horseradish peroxidase in polarised T84 cells, without affecting transepithelial electrical resistance. Conclusions: Our findings suggest increased endosomal uptake of antigens in ileal Crohn’s disease that may be mediated by TNF-α. These data highlight the transcellular route of antigen uptake in barrier dysfunction and implicate the interaction between epithelial cells and the innate immune system in the development of mucosal inflammation.
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Endocytotic exodus of microbes in barrier dysfunction Crohn's disease induces mucosal inflammation.
“Endocytotic exodus of microbes in the barrier dysfunction CD, induces mucosal inflammation [180,181].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [180]
Cites
Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat
Santos, J., Yang, P.-C., Söderholm, J. D., Benjamin, M., & Perdue, M. H. (2001) · Gut · doi:10.1136/gut.48.5.630 · Cited by 313 · see citing works
Self-citationIrvine, E. J., & Marshall, J. K. (2000) · Gastroenterology · doi:10.1053/gast.2000.20231 · Cited by 286 · see citing works
Stress stimulates transepithelial macromolecular uptake in rat jejunum
Kiliaan, A. J., Saunders, P. R., Bijlsma, P. B., Berin, M. C., Taminiau, J. A., Groot, J. A., & Perdue, M. H. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.275.5.g1037 · Cited by 223 · see citing works
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Thevaranjan, N., Puchta, A., Schulz, C., Naidoo, A., Szamosi, J. C., Verschoor, C. P., Loukov, D., Schenck, L. P., Jury, J., Foley, K. P., et al. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.03.002 · Cited by 1,322 · see citing works
Psychological stress in IBD: new insights into pathogenic and therapeutic implications
Mawdsley, J. E., & Rampton, D. S. (2005) · Gut · doi:10.1136/gut.2005.064261 · Cited by 622 · see citing works
Probiotics promote gut health through stimulation of epithelial innate immunity
Pagnini, C., Saeed, R., Bamias, G., Arseneau, K. O., Pizarro, T. T., & Cominelli, F. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910307107 · Cited by 358 · see citing works
Keita, Å. V., & Söderholm, J. D. (2010) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2010.01498.x · Cited by 286 · see citing works
Self-citationMawdsley, J. E., Macey, M. G., Feakins, R. M., Langmead, L., & Rampton, D. S. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.05.017 · Cited by 143 · see citing works
Heller, F., Fromm, A., Gitter, A. H., Mankertz, J., & Schulzke, J.-D. (2008) · Mucosal Immunology · doi:10.1038/mi.2008.46 · Cited by 135 · see citing works
Rath, T., Atreya, R., Bodenschatz, J., Uter, W., Geppert, C. E., Vitali, F., Fischer, S., Waldner, M. J., Colombel, J.-F., Hartmann, A., et al. (2023) · Gastroenterology · doi:10.1053/j.gastro.2022.10.014 · Cited by 133 · see citing works
Anti-TNF-α antibodies improve intestinal barrier function in Crohn's disease
Noth, R., Stüber, E., Häsler, R., Nikolaus, S., Kühbacher, T., Hampe, J., Bewig, B., Schreiber, S., & Arlt, A. (2012) · Journal of Crohn s and Colitis · doi:10.1016/j.crohns.2011.10.004 · Cited by 68 · see citing works
Insights of Endocytosis Signaling in Health and Disease
Pathak, C., Vaidya, F. U., Waghela, B. N., Jaiswara, P. K., Gupta, V. K., Kumar, A., Rajendran, B. K., & Ranjan, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032971 · Cited by 59 · see citing works
Stress-related changes in oesophageal permeability: filling the gaps of GORD?: Figure 1
Söderholm, J. D. (2007) · Gut · doi:10.1136/gut.2007.120691 · Cited by 25 · see citing works
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- Authors
- Söderholm, J. D., Streutker, C., Yang, P.-C., Paterson, C., Singh, P. K., McKay, D. M., Sherman, P. M., Croitoru, K., & Perdue, M. H.
- Affiliations
- Linköping University Hospital (SE)
- St. Michael's Hospital (CA)
- McMaster University (CA)
- University of Toronto (CA)
- Corresponding author
- Söderholm, J D
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2004-11-11
- Volume
- 53
- Issue
- 12
- Pages
- 1817-1824
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1774309
- OpenAlex
- W2110251267
- Cited by
- 160
- References
- 3
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 7
- FWCI
- 7.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Crohn's and Colitis Foundation
- Crohn's and Colitis Foundation of Canada
- Vetenskapsrådet
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Crohn's disease, TNF-α, intestinal epithelial barrier dysfunction, endocytosis, horseradish peroxidase, endosomes, ileum, T84 cells, transepithelial electrical resistance
- MeSH terms
- Adult, Antigens, Cell Line, Crohn Disease, Dose-Response Relationship, Drug, Female, Horseradish Peroxidase, Humans, Ileum, Intestinal Mucosa, Male, Middle Aged, Permeability, Endosomes, RNA, Messenger, Tumor Necrosis Factor-alpha
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