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Gastroenterology. 2008 Jan;134(1):204-14. doi: 10.1053/j.gastro.2007.10.002. Epub 2007 Oct 5.

Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia.

Author information

1
Division of Allergy and Immunology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Abstract

BACKGROUND & AIMS:

Eosinophilic esophagitis (EE) is an increasingly recognized disease that mimics gastroesophageal reflux disease. Recently, EE has been associated with esophageal remodeling, but the mechanisms involved are poorly understood. We hypothesized that the development of EE in patients and in an experimental murine model would be associated with eosinophil-mediated tissue remodeling.

METHODS:

Histopathologic analysis of basal layer thickness and collagen accumulation was performed on the biopsy specimens of normal individuals, EE patients, and mouse esophageal tissue sections following experimental induction of EE in wild-type, eosinophil lineage-deficient, interleukin (IL)-5-deficient, and IL-5 transgenic mice, with the latter 2 mice groups having decreased and increased esophageal eosinophilia, respectively.

RESULTS:

An impressive accumulation of collagen in the epithelial mucosa and lamina propria, as well as basal layer thickening, was observed in the esophagus of patients with EE as well as in mice with experimental EE compared with controls. Significantly reduced lamina propria collagen and basal layer thickness were observed in IL-5-deficient mice and eosinophil lineage-deficient mice compared with wild-type mice following the induction of experimental EE. Furthermore, the esophagus of CD2-IL-5 transgenic mice showed increased basal layer thickness and collagen accumulation compared with nontransgenic mice, yet IL-5 intestine transgenic mice did not have EE-like esophageal changes. Additional analysis revealed increased IL-5 levels in the esophagus of EE patients, allergen-challenged wild-type mice, and CD2-IL-5 transgenic mice but not in IL-5 intestine transgenic mice.

CONCLUSIONS:

These findings provide evidence that local IL-5-mediated eosinophilia is essential in the induction of esophageal remodeling.

PMID:
18166354
PMCID:
PMC2654267
DOI:
10.1053/j.gastro.2007.10.002
[Indexed for MEDLINE]
Free PMC Article

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