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

Joanne C. Masterson, Eóin N. McNamee, Lindsay Hosford, Kelley E. Capocelli, Joseph Ruybal, Sophie A. Fillon, Alfred D. Doyle, Holger K. Eltzschig, Anil K. Rustgi, Cheryl A. Protheroe, Nancy A Lee, James J. Lee, Glenn T. Furuta

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalGut
Volume63
Issue number1
DOIs
StatePublished - Jan 2014

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Eosinophilic Esophagitis
Interleukin-5
Transgenic Mice
Eosinophilia
Hypersensitivity
Eosinophils
Oxazolone
Esophagus
Chemokine CCL11
Interleukin-13
Human Herpesvirus 4
Chemokines
Hyperplasia
Adrenal Cortex Hormones
Theoretical Models
Epithelium
Inflammation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Masterson, J. C., McNamee, E. N., Hosford, L., Capocelli, K. E., Ruybal, J., Fillon, S. A., ... Furuta, G. T. (2014). Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis. Gut, 63(1), 43-53. https://doi.org/10.1136/gutjnl-2012-303631

Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis. / Masterson, Joanne C.; McNamee, Eóin N.; Hosford, Lindsay; Capocelli, Kelley E.; Ruybal, Joseph; Fillon, Sophie A.; Doyle, Alfred D.; Eltzschig, Holger K.; Rustgi, Anil K.; Protheroe, Cheryl A.; Lee, Nancy A; Lee, James J.; Furuta, Glenn T.

In: Gut, Vol. 63, No. 1, 01.2014, p. 43-53.

Research output: Contribution to journalArticle

Masterson, JC, McNamee, EN, Hosford, L, Capocelli, KE, Ruybal, J, Fillon, SA, Doyle, AD, Eltzschig, HK, Rustgi, AK, Protheroe, CA, Lee, NA, Lee, JJ & Furuta, GT 2014, 'Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis', Gut, vol. 63, no. 1, pp. 43-53. https://doi.org/10.1136/gutjnl-2012-303631
Masterson, Joanne C. ; McNamee, Eóin N. ; Hosford, Lindsay ; Capocelli, Kelley E. ; Ruybal, Joseph ; Fillon, Sophie A. ; Doyle, Alfred D. ; Eltzschig, Holger K. ; Rustgi, Anil K. ; Protheroe, Cheryl A. ; Lee, Nancy A ; Lee, James J. ; Furuta, Glenn T. / Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis. In: Gut. 2014 ; Vol. 63, No. 1. pp. 43-53.
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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.",
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N2 - 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.

AB - 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.

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