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
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: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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