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    Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis


    Masterson, Joanne C. and McNamee, Eóin N. and Hosford, Lindsay and Capocelli, Kelley E. and Ruybal, Joseph and Fillon, Sophie A. and Doyle, Alfred D. and Eltzschig, Holger K. and Rustgi, Anil K. and Protheroe, Cheryl and Lee, Nancy A. and Lee, James J. and Furuta, Glenn T. (2014) Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis. Gut, 63 (1). pp. 43-53. ISSN 1468-3288

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    Abstract

    Objective: Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition of the oesophagus with limited treatment options. No previous transgenic model has specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia. Design: We developed a mouse model that closely resembles EoE by utilising oxazolone haptenation in mice with transgenic overexpression of an eosinophil poietic and survival factor (interleukin (IL)-5) in resident squamous oesophageal epithelia. Results: Overexpression of IL-5 in the healthy oesophagus was achieved in transgenic mice (L2-IL5) using the squamous epithelial promoter Epstein–Barr virus ED-L2. Oxazolone-challenged L2-IL5 mice developed dose-dependent pan-oesophageal eosinophilia, including eosinophil microabscess formation and degranulation as well as basal cell hyperplasia. Moreover, oesophagi expressed increased IL-13 and the eosinophil agonist chemokine eotaxin-1. Treatment of these mice with corticosteroids significantly reduced eosinophilia and epithelial inflammation. Conclusions: L2-IL5 mice provide a novel experimental model that can potentially be used in preclinical testing of EoE-related therapeutics and mechanistic studies identifying pathogenetic features associated with mucosal eosinophilia.

    Item Type: Article
    Keywords: Local hypersensitivity; reaction; transgenic mice; squamous epithelial IL-5 overexpression; eosinophilic oesophagitis;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12487
    Identification Number: https://doi.org/10.1136/gutjnl-2012-303631
    Depositing User: Joanne Masterson
    Date Deposited: 26 Feb 2020 17:12
    Journal or Publication Title: Gut
    Publisher: BMJ Publishing Group
    Refereed: Yes
    URI:

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