Mend Your Fences: The Epithelial Barrier and its Relationship With Mucosal Immunity in Inflammatory Bowel Disease
TLDR
This review summarizes the important cellular and molecular barrier components of the intestinal epithelium and emphasizes the mechanisms leading to barrier dysfunction during intestinal inflammation.Abstract:
The intestinal epithelium can be easily disrupted during gut inflammation as seen in inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn's disease. For a long time, research into the pathophysiology of IBD has been focused on immune cell-mediated mechanisms. Recent evidence, however, suggests that the intestinal epithelium might play a major role in the development and perpetuation of IBD. It is now clear that IBD can be triggered by disturbances in epithelial barrier integrity via dysfunctions in intestinal epithelial cell-intrinsic molecular circuits that control the homeostasis, renewal, and repair of intestinal epithelial cells. The intestinal epithelium in the healthy individual represents a semi-permeable physical barrier shielding the interior of the body from invasions of pathogens on the one hand and allowing selective passage of nutrients on the other hand. However, the intestinal epithelium must be considered much more than a simple physical barrier. Instead, the epithelium is a highly dynamic tissue that responds to a plenitude of signals including the intestinal microbiota and signals from the immune system. This epithelial response to these signals regulates barrier function, the composition of the microbiota, and mucosal immune homeostasis within the lamina propria. The epithelium can thus be regarded as a translator between the microbiota and the immune system and aberrant signal transduction between the epithelium and adjacent immune cells might promote immune dysregulation in IBD. This review summarizes the important cellular and molecular barrier components of the intestinal epithelium and emphasizes the mechanisms leading to barrier dysfunction during intestinal inflammation.read more
Citations
More filters
Journal ArticleDOI
Shen-Ling-Bai-Zhu-San Improves Dextran Sodium Sulfate-Induced Colitis by Inhibiting Caspase-1/Caspase-11-Mediated Pyroptosis.
Li-min Chao,Li Zengquan,Jia-hao Zhou,Wen-qian Chen,Yuefei Li,Weijie Lv,Ao Guo,Qian Qu,Shining Guo +8 more
TL;DR: It is demonstrated that SLBZS attenuates DSS-induced ulcerative colitis injury in mice via the MAPK/NF-κB and pyroptosis signaling pathway, indicating that SLZS is a potential drug for the treatment of UC.
Journal ArticleDOI
Anti-Inflammatory and Barrier-Stabilising Effects of Myrrh, Coffee Charcoal and Chamomile Flower Extract in a Co-Culture Cell Model of the Intestinal Mucosa
TL;DR: The results provide a mechanistic basis for the use of the herbal combination of myrrh, coffee charcoal and chamomile flower extract in IBD treatment and underline the potential benefits of the phytotherapeutic multi-component/multi-target approach in this complex pathogenesis.
Journal ArticleDOI
IL-1R1–dependent signaling coordinates epithelial regeneration in response to intestinal damage
Christian Cox,Elaine E. Storm,Varun N. Kapoor,Joseph Chavarria-Smith,David L. Lin,Lifen Wang,Yun Li,Noelyn M. Kljavin,Naruhisa Ota,Travis W. Bainbridge,Keith R. Anderson,Merone Roose-Girma,Søren Warming,Joseph R. Arron,Shannon J. Turley,Frederic J. de Sauvage,Menno van Lookeren Campagne +16 more
TL;DR: This paper showed that after distinct types of intestinal epithelial damage, IL-1R1 signaling in GREM1+ mesenchymal cells increases production of R-spondin 3 (RSPO3), a Wnt agonist required for intestinal stem cell self-renewal.
Journal ArticleDOI
Fourteen composite probiotics alleviate type 2 diabetes through modulating gut microbiota and modifying M1/M2 phenotype macrophage in db/db mice.
Yanming Wang,Yuche Wu,Jialehasibieke Sailike,Xin Sun,Nigare Abuduwaili,Hapula Tuoliuhan,Mulatiaize Yusufu,Xin-Hua Nabi +7 more
TL;DR: Results showed that treatment with 14 composite probiotics improved intestinal microbiota equilibrium by increasing the population of short-chain fatty acids (SCFAs)-producing bacteria and decreasing the number of harmful bacteria, and indicate that the 14 composite Probiotics can potentially improve diabetes prognosis.
Journal ArticleDOI
Ginseng berry polysaccharides on inflammation-associated colon cancer: inhibiting T-cell differentiation, promoting apoptosis, and enhancing the effects of 5-fluorouracil
Chong-Zhi Wang,Lifei Hou,Jin-Yi Wan,Jin-Yi Wan,Haiqiang Yao,Jinbin Yuan,Jinxiang Zeng,Chan Woong Park,Chan Woong Park,Su Hwan Kim,Dae Bang Seo,Kwang-Soon Shin,Chun-Feng Zhang,Lina Chen,Qi-Hui Zhang,Zhi Liu,Clara Sava-Segal,Chun-Su Yuan +17 more
TL;DR: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.
References
More filters
Journal ArticleDOI
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Jean-Pierre Hugot,Mathias Chamaillard,Mathias Chamaillard,Habib Zouali,Suzanne Lesage,Jean-Pierre Cézard,Jacques Belaiche,Sven Almer,Curt Tysk,Colm O'Morain,Miquel A. Gassull,Vibeke Binder,Yigael Finkel,Antoine Cortot,Robert Modigliani,Pierre Laurent-Puig,C. Gower-Rousseau,J. Macry,Jean-Frederic Colombel,Mourad Sahbatou,Gilles Thomas,Gilles Thomas +21 more
TL;DR: It is suggested that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn’s disease that can now be further investigated.
Journal ArticleDOI
Identification of stem cells in small intestine and colon by marker gene Lgr5
Nick Barker,Johan H. van Es,Jeroen Kuipers,Pekka Kujala,Maaike van den Born,Miranda Cozijnsen,Andrea Haegebarth,Jeroen Korving,Harry Begthel,Peter J. Peters,Hans Clevers +10 more
TL;DR: The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers, suggesting that it represents the stem cell of the small intestine and colon.
Journal ArticleDOI
A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
Yasunori Ogura,Denise K. Bonen,Naohiro Inohara,Dan L. Nicolae,Felicia F. Chen,Richard Ramos,Heidi M. Britton,Thomas M. Moran,Reda Karaliuskas,Richard H. Duerr,Jean-Paul Achkar,Steven R. Brant,Theodore M. Bayless,Barbara S. Kirschner,Stephen B. Hanauer,Gabriel Núñez,Judy H. Cho +16 more
TL;DR: It is shown that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease, and a link between an innate immune response to bacterial components and development of disease is suggested.
Journal ArticleDOI
The Nuclear Factor NF-κB Pathway in Inflammation
TL;DR: How genetic evidence in mice has revealed complex roles for the NF-kappaB in inflammation that suggest both pro- and anti-inflammatory roles for this pathway is described.
Journal ArticleDOI
Defensins: antimicrobial peptides of innate immunity.
TL;DR: This review, inspired by a spate of recent studies ofdefensins in human diseases and animal models, focuses on the biological function of defensins.
Related Papers (5)
Intestinal epithelial cells: regulators of barrier function and immune homeostasis
Lance W. Peterson,David Artis +1 more