Detergent‐induced eosinophilic inflammation in the esophagus: A key evidence for the epithelial barrier theory

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BackgroundEpithelial barrier impairment is associated with many skin and mucosal inflammatory disorders. Laundry detergents have been demonstrated to affect epithelial barrier function in vitro using air–liquid interface cultures of human epithelial cells.MethodsBack skin of C57BL/6 mice was treated with two household laundry detergents at several dilutions. Barrier function was assessed by electric impedance spectroscopy (EIS) and transepidermal water loss (TEWL) measurements after the 4 h of treatments with detergents. RNA sequencing (RNA‐seq) and targeted multiplex proteomics analyses in skin biopsy samples were performed. The 6‐h treatment effect of laundry detergent and sodium dodecyl sulfate (SDS) was investigated on ex vivo human skin.ResultsDetergent‐treated skin showed a significant EIS reduction and TEWL increase compared to untreated skin, with a relatively higher sensitivity and dose–response in EIS. The RNA‐seq showed the reduction of the expression of several genes essential for skin barrier integrity, such as tight junctions and adherens junction proteins. In contrast, keratinization, lipid metabolic processes, and epidermal cell differentiation were upregulated. Proteomics analysis showed that the detergents treatment generally downregulated cell adhesion‐related proteins, such as epithelial cell adhesion molecule and contactin‐1, and upregulated proinflammatory proteins, such as interleukin 6 and interleukin 1 beta. Both detergent and SDS led to a significant decrease in EIS values in the ex vivo human skin model.ConclusionThe present study demonstrated that laundry detergents and its main component, SDS impaired the epidermal barrier in vivo and ex vivo human skin. Daily detergent exposure may cause skin barrier disruption and may contribute to the development of atopic diseases.

Section: Discussionmentioning

confidence: 99%

“…In addition, other daily products, such as toothpastes and dishwasher detergents, contain SDS. They may damage oral, esophageal, and gut epithelial barriers 53–55 . These daily cleaning products may induce barrier dysfunction especially in infant and allergic patients 6,56,57 .…”

Section: Discussionmentioning

confidence: 99%

Household laundry detergents disrupt barrier integrity and induce inflammation in mouse and human skin

Rinaldi,

Li,

Barletta

et al. 2023

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Section: Discussionmentioning

confidence: 99%

“…According to the epithelial barrier theory, many toxins and chemicals that humans are exposed to daily damage the epithelium on the surface of our skin, lungs, vagina, and intestine. 50 Defective epithelial barrier has been demonstrated in a wide range of allergic and autoimmune conditions. 51 Microbiota which normally float above the skin and mucosa goes deeper between and beneath damaged epithelial barrier, and colonization of opportunistic pathogens cause microbial dysbiosis.…”

Section: Eis/adscoreanddemographicandearly Life Factorsmentioning

confidence: 99%

Electrical impedance spectroscopy detects skin barrier dysfunction in childhood atopic dermatitis

Sasaki,

Sundberg,

Frei

et al. 2023

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BackgroundSkin barrier dysfunction is associated with the development of atopic dermatitis (AD), however methods to assess skin barrier function are limited. We investigated the use of electrical impedance spectroscopy (EIS) to detect skin barrier dysfunction in children with AD of the CARE (Childhood AlleRgy, nutrition, and Environment) cohort.MethodsEIS measurements taken at multiple time points from 4 months to 3‐year‐old children, who developed AD (n = 66) and those who did not (n = 49) were investigated. Using only the EIS measurement and the AD status, we developed a machine learning algorithm that produces a score (EIS/AD score) which reflects the probability that a given measurement is from a child with active AD. We investigated the diagnostic ability of this score and its association with clinical characteristics and age.ResultsBased on the EIS/AD score, the EIS algorithm was able to clearly discriminate between healthy skin and clinically unaffected skin of children with active AD (area under the curve 0.92, 95% CI 0.85–0.99). It was also able to detect a difference between healthy skin and AD skin when the child did not have active AD. There was no clear association between the EIS/AD score and the severity of AD or sensitisation to the tested allergens. The performance of the algorithm was not affected by age.ConclusionsThis study shows that EIS can detect skin barrier dysfunction and differentiate skin of children with AD from healthy skin and suggests that EIS may have the ability to predict future AD development.

“…A systemic IgE priming may also occur by exposing tape‐strip damaged epidermis to allergen, 96 with the exposure to allergens through eczematous skin lesions or a damaged epithelial barrier, such as occurs with filaggrin loss‐of‐function mutations that render individuals prone to atopic diseases, 97,98 potentially underlying sensitization, setting the epitopes that are recognized by IgE in allergic individuals 71 . Damage to epithelial barriers caused by detergents and environmental pollutants is a tenet of the “epithelial barrier” hypothesis, seen as a major cause of multiple diseases, including those mediated by type 2 immunity and associated with IgE 99–101 . A recently identified subset of dendritic cells responsive to IL‐13 that promotes type 2 immunity may be key to IgE production after allergen exposure through a compromised epithelial barrier, 102 but alarmins, such as IL‐33 likely also play a role 91,96 .…”

Section: How Does Sensitization Happen?mentioning

confidence: 99%

The origins and longevity of IgE responses as indicated by serological and cellular studies in mice and humans

Ding

Mulder

Robinson

2023

The existence of long‐lived IgE antibody‐secreting cells (ASC) is contentious, with the maintenance of sensitization by the continuous differentiation of short‐lived IgE+ ASC a possibility. Here, we review the epidemiological profile of IgE production, and give an overview of recent discoveries made on the mechanisms regulating IgE production from mouse models. Together, these data suggest that for most individuals, in most IgE‐associated diseases, IgE+ ASC are largely short‐lived cells. A subpopulation of IgE+ ASC in humans is likely to survive for tens of months, although due to autonomous IgE B cell receptor (BCR) signaling and antigen‐driven IgE+ ASC apoptosis, in general IgE+ ASC probably do not persist for the decades that other ASC are inferred to do. We also report on recently identified memory B cell transcriptional subtypes that are the likely source of IgE in ongoing responses, highlighting the probable importance of IL‐4Rα in their regulation. We suggest the field should look at dupilumab and other drugs that prohibit IgE+ ASC production as being effective treatments for IgE‐mediated aspects of disease in most individuals.