Elsevier

Mucosal Immunology

Volume 7, Issue 3, May 2014, Pages 718-729
Mucosal Immunology

Article
Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis

https://doi.org/10.1038/mi.2013.90Get rights and content
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Abstract

The desmosomal cadherin desmoglein-1 (DSG1) is an essential intercellular adhesion molecule that is altered in various human cutaneous disorders; however, its regulation and function in allergic disease remains unexplored. Herein, we demonstrate a specific reduction in DSG1 in esophageal biopsies from patients with eosinophilic esophagitis (EoE), an emerging allergic disorder characterized by chronic inflammation within the esophageal mucosa. Further, we show that DSG1 gene silencing weakens esophageal epithelial integrity, and induces cell separation and impaired barrier function (IBF) despite high levels of desmoglein-3. Moreover, DSG1 deficiency induces transcriptional changes that partially overlap with the transcriptome of inflamed esophageal mucosa; notably, periostin (POSTN), a multipotent pro-inflammatory extracellular matrix molecule, is the top induced overlapping gene. We further demonstrate that IBF is a pathological feature in EoE, which can be partially induced through the downregulation of DSG1 by interleukin-13 (IL-13). Taken together, these data identify a functional role for DSG1 and its dysregulation by IL-13 in the pathophysiology of EoE and suggest that the loss of DSG1 may potentiate allergic inflammation through the induction of pro-inflammatory mediators such as POSTN.

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Published online: 13 November 2013

SUPPLEMENTARY MATERIAL is linked to the online version of the paper

Supplementary information The online version of this article (doi:10.1038/mi.2013.90) contains supplementary material, which is available to authorized users.