Dataset Information

IL-33 is induced in undifferentiated, non-dividing esophageal epithelial cells in eosinophilic esophagitis.

ABSTRACT: The molecular and cellular etiology of eosinophilic esophagitis (EoE), an emerging tissue-specific allergic disease, involves dysregulated gene expression in esophageal epithelial cells. Herein, we assessed the esophageal expression of IL-33, an epithelium-derived alarmin cytokine, in patients with EoE. IL-33 protein was markedly overexpressed within the nuclei of a subpopulation of basal layer esophageal epithelial cells in patients with active EoE compared to control individuals. IL-33 exhibited dynamic expression as levels normalized upon EoE remission. IL-33-positive basal epithelial cells expressed E-cadherin and the undifferentiated epithelial cell markers keratin 5 and 14 but not the differentiation marker keratin 4. Moreover, the IL-33-positive epithelial cells expressed the epithelial progenitor markers p75 and p63 and lacked the proliferation markers Ki67 and phospho-histone H3. Additionally, the IL-33-positive cells had low expression of PCNA. IL-33 expression was detected in ex vivo-cultured primary esophageal epithelial cells in a subpopulation of cells lacking expression of proliferation markers. Collectively, we report that IL-33 expression is induced in an undifferentiated, non-dividing esophageal epithelial cell population in patients with active EoE.

SUBMITTER: Travers J

PROVIDER: S-EPMC5730585 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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IL-33 is induced in undifferentiated, non-dividing esophageal epithelial cells in eosinophilic esophagitis.

Travers J J Rochman M M Caldwell J M JM Besse J A JA Miracle C E CE Rothenberg M E ME

Scientific reports 20171214 1

The molecular and cellular etiology of eosinophilic esophagitis (EoE), an emerging tissue-specific allergic disease, involves dysregulated gene expression in esophageal epithelial cells. Herein, we assessed the esophageal expression of IL-33, an epithelium-derived alarmin cytokine, in patients with EoE. IL-33 protein was markedly overexpressed within the nuclei of a subpopulation of basal layer esophageal epithelial cells in patients with active EoE compared to control individuals. IL-33 exhibit ...[more]

PMID: 29242581

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Project description:Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory disease of the esophagus characterized predominantly by eosinophilic inflammation, leading to esophageal dysfunction. Converging data have placed the esophageal epithelium at the center of disease pathogenesis. In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively. Furthermore, genetic and functional data establish a primary role for impaired epithelial barrier function in disease susceptibility and pathoetiology. Additionally, the EoE transcriptome, a set of genes dysregulated in the esophagi of patients with EoE, is enriched in genes that encode for proteins involved in esophageal epithelial cell differentiation. This transcriptome has a high proportion of esophagus-specific epithelial genes that are notable for the unexpected enrichment in genes encoding for proteases and protease inhibitors, as well as in IL-1 family genes, demonstrating a previously unappreciated role for innate immunity responses in the esophagus under homeostatic conditions. Among these pathways, basal production of the serine protease inhibitor, Kazal-type 7 (SPINK7) has been demonstrated to be part of the normal differentiation program of esophageal epithelium. Profound lost expression of SPINK7 occurs in patients with EoE and is sufficient for unleashing increased proteolytic activity (including urokinase plasminogen activator), impaired barrier function, and production of large quantities of proinflammatory and proallergic cytokines, including thymic stromal lymphopoietin. Collectively, we put forth a model in which the esophagus is normally equipped as an anti-inflammatory sensing organ and that defects in this pathway, mediated by epithelial protease/protease inhibitor imbalances, unleash inflammatory responses resulting in disorders, such as EoE.

Dataset Information

IL-33 is induced in undifferentiated, non-dividing esophageal epithelial cells in eosinophilic esophagitis.

Publications

IL-33 is induced in undifferentiated, non-dividing esophageal epithelial cells in eosinophilic esophagitis.

Similar Datasets

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