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Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis.
Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2014 May; Vol. 7 (3), pp. 718-29. Date of Electronic Publication: 2013 Nov 13. - Publication Year :
- 2014
-
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.
- Subjects :
- Cell Differentiation genetics
Cluster Analysis
Desmoglein 1 deficiency
Desmoglein 1 genetics
Eosinophilic Esophagitis genetics
Epithelial Cells cytology
Epithelial Cells metabolism
Gene Expression Profiling
Gene Expression Regulation
Gene Knockdown Techniques
Humans
Immunity, Innate genetics
Immunohistochemistry
Interleukin-13 metabolism
Models, Biological
Mucous Membrane pathology
Transcription, Genetic
Desmoglein 1 metabolism
Eosinophilic Esophagitis immunology
Eosinophilic Esophagitis metabolism
Mucous Membrane immunology
Mucous Membrane metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 24220297
- Full Text :
- https://doi.org/10.1038/mi.2013.90