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. 2019 Feb;68(2):225-231.
doi: 10.1097/MPG.0000000000002144.

Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis

Ashmi Doshi  1   2   3 , Rebecca Khamishon  1   2   3 , Renee Rawson  1   2 , Loan Duong  1   2 , Lucas Dohil  1   2 , Stephen J Myers  1   2   3 , Braxton Bell  1   2 , Ranjan Dohil  4   2 , Robert O Newbury  2   5 , Kim E Barrett  1   4   3 , Richard C Kurten  6 , Seema S Aceves  1   2   3
Affiliations

Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis

Ashmi Doshi et al. J Pediatr Gastroenterol Nutr. 2019 Feb.

Abstract

Background: Eosinophilic esophagitis (EoE) is a chronic TH2-assocated inflammatory condition accompanied by substantial impairments in epithelial barrier function and increased numbers of interleukin 9 (IL-9) expressing inflammatory cells. While IL-9 is known to affect barrier function in the intestine, the functional effects of IL-9 on the esophagus are unclear. Herein we aimed to understand the expression of the IL-9 receptor and effects of IL-9 on the epithelium in EoE.

Methods: We used esophageal biopsies from pediatric EoE patients with active and inactive disease to analyze the expression of the IL-9 receptor, the adherens junction protein E-cadherin and the tight junction protein claudin-1. We treated primary human esophageal epithelial cells with IL-9 to understand its effects on E-cadherin expression and function.

Results: Active EoE subjects had increased epithelial expression of IL-9 receptor mRNA and protein (P < 0.05) and decreased membrane bound E-cadherin (P < 0.01) and claudin-1 (P < 0.05) expression. IL-9 receptor expression and mislocalized claudin-1 positively correlated and while membrane bound E-cadherin expression negatively correlated with the degree of histologic epithelial remodeling (P < 0.05). IL-9 decreased epithelial resistance in stratified primary human esophageal epithelial cells (P < 0.01) and membrane bound E-cadherin in epithelial cell monolayers (P < 0.01).

Conclusions: These data suggest that IL-9, its receptor, and its effects on E-cadherin may be important mechanisms for epithelial barrier disruption in EoE.

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Conflict of interest statement

The authors have no relevant conflicts of interest

Figures

Figure 1.
Figure 1.. IL-9 receptor (IL-9R) expression in EoE.
Representative images (A) and quantitation (B) of IL-9R positive cells in the esophageal epithelium of active and inactive EoE biopsies. Inset in inactive biopsy shows isotype control on an active EoE biopsy. Lines represent mean and standard deviation. The correlation between IL-9R expression and epithelial remodeling (C). Normalized IL-9R mRNA expression in active and inactive biopsies. Bars represent the mean and standard deviation (D).
Figure 2.
Figure 2.. E-cadherin expression in EoE.
Representative images of E-cadherin in control (A), inactive, and active EoE (B). Quantitation of membrane bound E-cadherin in active and inactive EoE. Lines represent means, bars are standard deviation (C). Correlation between the severity of esophageal epithelial remodeling and membrane bound E-cadherin (D)
Figure 3.
Figure 3.. Claudin-1 expression in the EoE.
Representative images of claudin-1 in control (A), active, and inactive EoE (B) esophageal biopsies. Quantitation of the ratio of cytoplasmic : membrane- bound claudin-1 in active and inactive EoE Lines represent means, bars are standard deviation (C) and its correlation with the severity of epithelial remodeling (D).
Figure 4.
Figure 4.. IL-9 effects on esophageal epithelial barrier and E-cadherin.
Representative image of stratified primary esophageal epithelial cells epithelium on transwells (A) and transepithelial resistance following treatment with IL-9 or vehicle. Bars represent mean and standard deviation (B). Representative image (C) and quantitation of membrane bound E-cadherin expression on cultured epithelial cells treated with vehicle or IL-9. Bars represent means and standard deviations (D).
See this image and copyright information in PMC

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