Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid‐treated eosinophilic esophagitis

Simon, Dagmar; Page, Basile; Vogel, Monique; Bussmann, Christian; Blanchard, Carine; Straumann, Alex; Simon, Hans‐Uwe

doi:10.1111/all.13244

Cited by 69 publications

(86 citation statements)

References 40 publications

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“…The pathophysiology of EoE is thought to arise from the presence of food allergens in contact with the esophageal mucosa, which causes a T‐helper type 2 (Th2) immune response leading to mucosal inflammation and eosinophilia, epithelial dysfunction, and long‐term fibrosis . Epithelial barrier dysfunction plays a critical role in this process because it promotes continued exposure to allergens and microbiota in the esophageal lumen, which stimulates epithelial cells and leukocytes to release chemokines and cytokines . Decreased barrier integrity in EoE has been measured by loss of mucosal impedance in vivo and transepithelial electrical resistance in vitro …”

Section: Introductionmentioning

confidence: 99%

“…The tight junction (TJ) complex is a dynamic structure comprised of transmembrane claudins, occludin, and cytosolic proteins (ie, zonula occludens‐1, zonula occludens‐2, and zonula occludens‐3), which connect the TJ to the cytoskeleton . Expression of occludin and claudin‐1 is decreased in biopsy tissue of EoE patients both before and after treatment with swallowed corticosteroid . In addition to tight junctions, multiple structural proteins contribute to the integrity and stratification of the esophageal epithelial barrier.…”

Section: Introductionmentioning

confidence: 99%

“…1 Epithelial barrier dysfunction plays a critical role in this process because it promotes continued exposure to allergens and microbiota in the esophageal lumen, which stimulates epithelial cells and leukocytes to release chemokines and cytokines. 2,3 Decreased barrier integrity in EoE has been measured by loss of mucosal impedance in vivo and transepithelial electrical resistance in vitro. [4][5][6] The loss of epithelial barrier integrity in EoE is attributed to the downregulation of important structural proteins in the inflamed mucosa including tight junction (TJ) proteins.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] The loss of epithelial barrier integrity in EoE is attributed to the downregulation of important structural proteins in the inflamed mucosa including tight junction (TJ) proteins. 2,5,7 The tight junction (TJ) complex is a dynamic structure comprised of transmembrane claudins, occludin, and cytosolic proteins (ie, zonula occludens-1, zonula occludens-2, and zonula occludens-3), which connect the TJ to the cytoskeleton. [8][9][10] Expression of occludin and claudin-1 is decreased in biopsy tissue of EoE patients both before and after treatment with swallowed corticosteroid.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] Expression of occludin and claudin-1 is decreased in biopsy tissue of EoE patients both before and after treatment with swallowed corticosteroid. 2 In addition to tight junctions, multiple structural proteins contribute to the integrity and stratification of the esophageal epithelial barrier. For example, recent descriptions of kindreds with biallelic mutations in DSG1 and DSP implicate desmosomes as a critical structural protein in the esophageal epithelium.…”

Section: Introductionmentioning

confidence: 99%

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Toll‐like receptor 2 stimulation augments esophageal barrier integrity

Ruffner

Song

Maurer

et al. 2019

Allergy

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Background: Germline-encoded innate immune pattern recognition receptors (PRR) are expressed at epithelial surfaces and modulate epithelial defenses. Evidence suggests that stimulation of the Toll-like receptor (TLR) family of PRR may regulate epithelial barrier integrity by upregulating tight junction (TJ) complex protein expression, but it is not known whether this mechanism is utilized in esophageal epithelial cells.TJ complex proteins maintain intact barrier function and are dysregulated in atopic disorders including eosinophilic esophagitis. Methods: Pattern recognition receptors expression was assessed in EoE and controlprimary esophageal epithelial cells, demonstrating robust expression of TLR2 and TLR3. The three-dimensional air-liquid interface culture (ALI) model was used to test whether TLR2 or TLR3 stimulation alters epithelial barrier function using an in vitro model of human epithelium. Transepithelial electrical resistance (TEER) and FITC-Dextran permeability were evaluated to assess membrane permeability. ALI cultures were evaluated by histology, immunohistochemistry, Western blotting, and chromatin immunoprecipitation (ChIP).Results: TLR3 stimulation did not change TEER in the ALI model. TLR2 stimulation increased TEER (1.28-to 1.31-fold) and decreased paracellular permeability to FITC-Dextran, and this effect was abolished by treatment with anti-TLR2 blocking antibody. TJ complex proteins claudin-1 and zonula occludens-1 were upregulated following TLR2 stimulation, and ChIP assay demonstrated altered histone 4 acetyl binding at the TJP1 enhancer and CLDN1 enhancer and promoter following zymosan treatment, implying the occurrence of durable chromatin changes. Conclusions:Our findings implicate the TLR2 pathway as a potential regulator of esophageal epithelial barrier function and suggest that downstream chromatin modifications are associated with this effect. K E Y W O R D Seosinophilic esophagitis, epithelium, innate immunity, tight junctions, toll-like receptors

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Toll‐like receptor 2 stimulation augments esophageal barrier integrity

Ruffner

Song

Maurer

et al. 2019

Allergy

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The Chemical and Social Landscape of the Modern World and Increased Risk ofASIA

Pinhasov,

Shmerkin,

Kirby

2024

Autoimmune Disorders

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Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

Sugita

Kabashima

2020

Journal of Leukocyte Biology

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This review focuses on recent developments related to asthma, chronic rhinosinusitis, atopic dermatitis (AD), eosinophilic esophagitis, and inflammatory bowel diseases (IBD), with a particular focus on tight junctions (TJs) and their role in the pathogenetic mechanisms of these diseases. Lung, skin, and intestinal surfaces are lined by epithelial cells that interact with environmental factors and immune cells. Therefore, together with the cellular immune system, the epithelium performs a pivotal role as the first line physical barrier against external antigens. Paracellular space is almost exclusively sealed by TJs and is maintained by complex protein-protein interactions. Thus, TJ dysfunction increases paracellular permeability, resulting in enhanced flux across TJs. Epithelial TJ dysfunction also causes immune cell activation and contributes to the pathogenesis of chronic lung, skin, and intestinal inflammation. Characterization of TJ protein alteration is one of the key factors for enhancing our understanding of allergic diseases as well as IBDs. Furthermore, TJ-based epithelial disturbance can promote immune cell behaviors, such as those in dendritic cells, Th2 cells, Th17 cells, and innate lymphoid cells (ILCs), thereby offering new insights into TJ-based targets. The purpose of this review is to illustrate how TJ dysfunction can lead to the disruption of the immune homeostasis in barrier tissues and subsequent inflammation.This review also highlights the various TJ barrier dysfunctions across different organ sites, which would help to develop future drugs to target allergic diseases and IBD.

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Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid‐treated eosinophilic esophagitis

Abstract: This study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote C. albicans colonization and likely subsequent sensitization.

Cited by 69 publications

References 40 publications

Toll‐like receptor 2 stimulation augments esophageal barrier integrity

Toll‐like receptor 2 stimulation augments esophageal barrier integrity

The Chemical and Social Landscape of the Modern World and Increased Risk ofASIA

Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

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