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
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Cocaine Induces Inflammatory Gut Milieu by Compromising the Mucosal Barrier Integrity and Altering the Gut Microbiota Colonization.
Ernest T. Chivero,Rizwan Ahmad,Annadurai Thangaraj,Palsamy Periyasamy,Balawant Kumar,Elisa Kroeger,Dan Feng,Minglei Guo,Sabita Roy,Punita Dhawan,Amar B. Singh,Shilpa Buch +11 more
TL;DR: It is confirmed that cocaine administration in mice resulted in alterations of the gut microbiota and cocaine-mediated gut dysbiosis was associated with upregulation of proinflammatory mediators including NF-κB and IL-1β.
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Butyrate Does Not Protect Against Inflammation-induced Loss of Epithelial Barrier Function and Cytokine Production in Primary Cell Monolayers From Patients With Ulcerative Colitis
Maaike Vancamelbeke,Thessa Laeremans,Wiebe Vanhove,Kaline Arnauts,Anabela S. Ramalho,Ricard Farré,Isabelle Cleynen,Marc Ferrante,Severine Vermeire +8 more
TL;DR: It is found that butyrate does not protect against inflammation-induced barrier dysfunction and even worsens its effects in primary epithelial monolayers of patients with ulcerative colitis and controls.
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The multiple faces of inflammatory enteric glial cells: is Crohn’s disease a gliopathy?
Camille Pochard,Sabrina Coquenlorge,Sabrina Coquenlorge,Marie Freyssinet,Marie Freyssinet,Philippe Naveilhan,Philippe Naveilhan,Arnaud Bourreille,Arnaud Bourreille,Michel Neunlist,Michel Neunlist,Malvyne Rolli-Derkinderen,Malvyne Rolli-Derkinderen +12 more
TL;DR: The aim of the present study is to review the physiological roles and properties of EGC, their response to inflammation, and their role in the regulation of the intestinal epithelial barrier and to discuss the emerging concept of CD as an enteric gliopathy.
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Subsets of mononuclear phagocytes are enriched in the inflamed colons of patients with IBD
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TL;DR: An extensive analysis of immune cell populations in IBD patient colonic samples and identified enriched subsets of monocytes, macrophages and dendritic cells in inflamed tissues that correlates with disease severity.
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Lychee (Litchi chinensis Sonn.) Pulp Phenolics Activate the Short-Chain Fatty Acid-Free Fatty Acid Receptor Anti-inflammatory Pathway by Regulating Microbiota and Mitigate Intestinal Barrier Damage in Dextran Sulfate Sodium-Induced Colitis in Mice.
Guitao Huang,Zhineng Wang,Guangxu Wu,Ruifen Zhang,Lihong Dong,Fei Huang,Mingwei Zhang,Dongxiao Su +7 more
TL;DR: Data indicate that LPP ameliorates gut barrier damage, activates the microbiota-SCFA-FFAR signaling cascade, and suppresses the TLR4/NLRP3-NF-κB pathway, and therefore, LPP supplementation could be a promising way to protect the intestinal tract.
References
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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.
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