Dysregulation of the epithelial barrier by environmental and other exogenous factors

Abstract

The "epithelial barrier hypothesis" proposes that the exposure to various epithelial barrier-damaging agents linked to industrialization and urbanization underlies the increase in allergic diseases. The epithelial barrier constitutes the first line of physical, chemical, and immunological defense against environmental factors. Recent reports have shown that industrial products disrupt the epithelial barriers. Innate and adaptive immune responses play an important role in epithelial barrier damage. In addition, recent studies suggest that epithelial barrier dysfunction plays an essential role in the pathogenesis of the atopic march by allergen sensitization through the transcutaneous route. It is evident that external factors interact with the immune system, triggering a cascade of complex reactions that damage the epithelial barrier. Epigenetic and microbiome changes modulate the integrity of the epithelial barrier. Robust and simple measurements of the skin barrier dysfunction at the point-of-care are of significant value as a biomarker, as recently reported using electrical impedance spectroscopy to directly measure barrier defects. Understanding epithelial barrier dysfunction and its mechanism is key to developing novel strategies for the

Characterization of eosinophilic esophagitis variants by clinical, histological, and molecular analyses: A cross‐sectional multi‐center study

“…Nevertheless, recent data—at least in EoE—suggest that an epithelial barrier defect leads to colonization with pathogens, subsequent sensitization, and possibly resulting in activation of eosinophils 22,23 . In addition, several environmental factors have been proposed to induce increased epithelial leakage, and a role of epithelial barrier defect has been suggested for previously considered functional gastrointestinal diseases 27–31 . Taken together, epithelial barrier disruption and TSLP upregulation—despite an otherwise attenuated Th2 signal and defects in eosinophil chemoattraction—appear to be key events in EoE variants clearly shifting away the focus from classical diagnostic approaches based on eosinophil‐associated proteins 32 …”

“…22,23 In addition, several environmental factors have been proposed to induce increased epithelial leakage, and a role of epithelial barrier defect has been suggested for previously considered functional gastrointestinal diseases. [27][28][29][30][31] Our study also has some limitations. GERD has not been rigorously excluded by pH testing in all patients.…”

How Do Pollen Allergens Sensitize?

“…The quantity of allergens transferred through the epithelia depends on the barrier integrity. A disturbed barrier function promotes allergic sensitization forming the “epithelial barrier hypothesis” ( Mitamura et al, 2021 ). Along these lines, different pollen species have been demonstrated to possess enzymatic activity reducing the epithelial integrity ( Gunawan et al, 2008 ; Van Cleemput et al, 2019 ; Bradbury et al, 2022 ).…”

Claudin-1 Mediated Tight Junction Dysfunction as a Contributor to Atopic March

“…Specifically, the synergic effect of CLDN-1 gene polymorphism and environmental factors, including lifestyles ( 117 ), infections ( 118 ) or pollutants ( 119 ) mediate the downregulation of claudin-1 in the epithelium of skin, airways, and GI tract, causing epithelial barrier dysfunction in these organs. Entry of allergens through damaged skin barrier leads to the systemic type 2 inflammation in patients with AD, which further downregulates the claudin-1 expression level in the GI tract and airways.…”