Dysregulation of the Epithelial Barrier by Environmental and Other Exogenous Factors

Overview

Journal Contact Dermatitis

Publisher Wiley

Specialty Dermatology

Date 2021 Aug 22

PMID 34420214

Citations 26

Authors

Yasutaka Mitamura

Ismail Ogulur

Yagiz Pat

Arturo O Rinaldi

Ozge Ardicli

Lacin Cevhertas

Marie-Charlotte Bruggen

Claudia Traidl-Hoffmann

Mubeccel Akdis

Cezmi A Akdis

Affiliations

Soon will be listed here.

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 prevention and treatment of allergic diseases. The aim of this review is to summarize recent studies on the pathophysiological mechanisms triggered by environmental factors that contribute to the dysregulation of epithelial barrier function.

Citing Articles

Type 2 immunity in allergic diseases.

Ogulur I, Mitamura Y, Yazici D, Pat Y, Ardicli S, Li M Cell Mol Immunol. 2025; 22(3):211-242.

PMID: 39962262 PMC: 11868591. DOI: 10.1038/s41423-025-01261-2.

Butyric acid alleviates LPS-induced intestinal mucosal barrier damage by inhibiting the RhoA/ROCK2/MLCK signaling pathway in Caco2 cells.

Liu L, Chen T, Xie Z, Zhang Y, He C, Huang Y PLoS One. 2024; 19(12):e0316362.

PMID: 39724098 PMC: 11670954. DOI: 10.1371/journal.pone.0316362.

Epithelial barrier dysfunction and associated diseases in companion animals: Differences and similarities between humans and animals and research needs.

Ardicli S, Ardicli O, Yazici D, Pat Y, Babayev H, Xiong P Allergy. 2024; 79(12):3238-3268.

PMID: 39417247 PMC: 11657079. DOI: 10.1111/all.16343.

The epithelial barrier theory and its associated diseases.

Sun N, Ogulur I, Mitamura Y, Yazici D, Pat Y, Bu X Allergy. 2024; 79(12):3192-3237.

PMID: 39370939 PMC: 11657050. DOI: 10.1111/all.16318.

Deciphering the Interplay between the Epithelial Barrier, Immune Cells, and Metabolic Mediators in Allergic Disease.

Kan L, Li P, Hon S, Lai A, Li A, Wong K Int J Mol Sci. 2024; 25(13).

PMID: 39000023 PMC: 11241838. DOI: 10.3390/ijms25136913.

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