Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus
Year: 2022
Type: article
Abstract: Background Eosinophilic esophagitis (EoE) is a chronic allergic disease associated with type 2 inflammation and epithelial barrier dysfunction. The etiology is unknown, however, genetic heritability studies suggest environmental factors play a key role in pathogenesis. Detergents, such as sodium dodecyl sulfate (SDS), are common ingredients in household products such as dish soap and toothpaste. We hypothesized detergent exposure decreases epithelial barrier function and induces esophageal inflammation. Methods Immortalized esophageal epithelial cells (EPC2) were cultured in air‐liquid interface (ALI) and exposed to SDS. Barrier function/activity was assessed by transepithelial electrical resistance (TEER), FITC‐dextran flux, and RT‐PCR. Additionally, SDS‐treated mouse esophageal organoids were evaluated for morphology. To investigate the effects of SDS in vivo, mice were treated with 0.5% SDS in drinking water for 14 days. Esophagi were assessed by gross morphology, histopathology, protein expression, and bulk RNA sequencing. Results When EPC2 cells were exposed to SDS (5 μg/ml) for 96 h, TEER decreased (p = 0.03), and FITC‐dextran flux increased (p = 0.0002). mRNA expression of IL‐33 increased 4.5‐fold (p = 0.02) at 6 h and DSG1 decreased (p < 0.0001) by 72 h. Disrupted epithelial integrity was noted in SDS‐treated esophageal organoids. When mice were exposed to SDS, they showed increased esophageal width, chemokine, and metalloprotease levels. Mice treated with SDS also showed increased IL‐33 protein expression, basal zone hyperplasia, CD4+ cell infiltration, and esophageal eosinophilia. RNA sequencing revealed upregulation of immune response pathway genes. Conclusion Exposure to SDS decreases esophageal barrier integrity, stimulates IL‐33 production, and promotes epithelial hyperplasia and tissue eosinophilia. Detergents may be a key environmental trigger in EoE pathogenesis.
Source: Allergy
DOI: 10.1111/all.15457
Language: English
Topic: Eosinophilic Esophagitis
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Mayo Clinic, American Partnership for Eosinophilic Disorders, Phoenix Children's Hospital, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: Consortium of Eosinophilic Gastrointestinal Disease Researchers, G2064554349, Autophagy and esophageal tissue remodeling in EoE, Type 2 Innate Lymphoid Cells and Asthma, Mechanisms of IL-33 secretion in allergic diseases, Data Management and Coordinating Center: Rare Diseases Clinical Research Network, Aldh2 and epithelial homeostasis and pathobiology, Mechanisms of Allergen-induced Type 2 Immunity, The Columbia University Digestive and Liver Disease Research Center
OpenAlex ID: W4288080565