Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis

Masterson, Joanne C.; Biette, Kathryn A.; Hammer, Juliet; Nguyen, Nathalie; Capocelli, Kelley E.; Saeedi, Bejan; Harris, Rachel; Fernando, Shahan D.; Hosford, Lindsay; Kelly, Caleb; Campbell, Eric L.; Ehrentraut, Stefan; Ahmed, Faria; Nakagawa, Hiroshi; Lee, James J.; McNamee, Eóin N.; Glover, Louise; Colgan, Sean P.; Furuta, Glenn T.

doi:10.1172/jci126744

Cited by 65 publications

(76 citation statements)

References 51 publications

(62 reference statements)

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“…In addition to TJ, reduced expression of filaggrin and desmoglein‐1 were noted in eosinophilic esophagitis 143 . Recently, hypoxia‐associated transcription factor HIF‐1α orchestrated epithelial barrier integrity, selectively regulating claudin‐1 144 . Thus, HIF‐1α and claudin‐1 axis can be a therapeutic target of eosinophilic esophagitis 144 .…”

Section: Tight Junction In Eosinophilic Esophagitismentioning

confidence: 99%

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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Section: Tight Junction In Eosinophilic Esophagitismentioning

confidence: 99%

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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“…Several studies have demonstrated that the oesophageal epithelial barrier function in patients with EoE in the active state is perturbed. The types of studies that support this include demonstration of increased permeability in Ussing chambers, 8 increased conductivity of the mucosa reflected through a decrease in electrical impedance measurement, 9,10 decreased detection of tight junction proteins in the oesophageal epithelium 11‐13 and dilation of intercellular spaces 9,14 . Indeed, dilation of intercellular spaces is a histologic hallmark of active EoE and one of the key elements of the recently developed histologic scoring system for EoE 14 .…”

Section: Discussionmentioning

confidence: 99%

Mucosal penetration and clearance of gluten and milk antigens in eosinophilic oesophagitis

Ravi

Marietta

Alexander

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundThe Th2 allergic pathway in eosinophilic oesophagitis (EoE) responds to food antigen exposure.AimTo compare the presence and temporal pattern of food antigen penetration in oesophageal mucosa in active and inactive EoE and controlsMethodsThirty‐two patients with EoE (20 active) and 10 controls were asked to eliminate all wheat and/or dairy 12, 24, 48, 72 or 96 hours before endoscopy. Immunostaining on endoscopic biopsies was performed for gliadin, casein and whey.ResultsGluten, casein and whey were detected by positive staining in 17/32 (53.1%), 21/32 (65.6%), and 30/32 (92.0%) of patients, respectively. In active vs inactive EoE, 70.0% vs 25.0% (P < 0.05), 80.0% vs 41.5%, and 90.0% vs 90.9% patients had detectable gliadin, casein and whey, respectively. Casein and whey (20.0% and 100%, respectively) but not gliadin, were present in controls. The gliadin staining density was greater in active compared to inactive disease at ≤ 24 vs >24 hours after exposure (P = 0.05) but no differences were detected when comparing active and inactive patients for casein and whey. There was greater staining density for whey than casein for all patients at ≤24 hours (mean 2.14 ± 0.91 and 1.07 ± 1.33, P = 0.02). In active EoE, IgG4 was present in 14/20 compared to one inactive patient.ConclusionThe oesophageal epithelium is selectively permeable and has relatively long dwell times for food antigens known to trigger EoE. The precise mechanism of antigen‐specific mucosal entry and the factors that determine the induction or effector trigger of the Th2 pathway activation merit further study.

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“…Both type 1 and 2 inflammations in the bronchus, gut, skin, esophagus, and sinus have indicated an effect of the opening of the epithelial barrier. 49,[55][56][57][58][59][60][61][62][63][64][65] Open epithelial TJ barrier in the mucosa allows pollutants, allergens, toxins, and any foreign substances to deeper tissues, 63 which eventually initiate local tissue inflammation. Currently, there are substantial data reporting that pollutants such as cigarette smoke, particulate matter, diesel exhaust, ozone, nanoparticles, microplastic, detergents, and cleaning agents and chemicals in household substances damage the epithelial barrier.…”

Section: Epithelium and The Environmentmentioning

confidence: 99%

The origins of allergy from a systems approach

Krempski

Dant

Nadeau

2020

Annals of Allergy, Asthma & Immunology

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Allergy in its various manifestations is a systems disease consisting of networks among multiple organs. The epithelium plays a central role in allergic disorders, and allergic sensitization occurs through the skin unless tolerance is induced through the gastrointestinal tract. Filaggrin loss-of-function mutations result in impaired epithelial barrier integrity and are substantial genetic risk factors for atopic dermatitis, asthma, allergic rhinitis, and food allergy in children. Dysregulated growth and repair pathways and interplay between airway epithelium asthma gene loci and viral, allergen, or microbial exposure are substantial factors for early-onset asthma development and exacerbation. As a critical sensor of environmental stimuli, the epithelia of the lungs, gut, and skin are affected by an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents, all of which account for an increase in the prevalence of allergic diseases. A beneficial diverse microbiome is critical in protecting against allergic diseases, and early oral exposure to food allergens are effective at preventing specific food allergies.

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Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis

Cited by 65 publications

References 51 publications

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

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

Mucosal penetration and clearance of gluten and milk antigens in eosinophilic oesophagitis

The origins of allergy from a systems approach

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