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Pathogenesis of allergen-induced eosinophilic esophagitis is independent of interleukin (IL)-13.

Abstract
Several studies have shown that interleukin (IL)-13 is induced in the esophageal biopsies of eosinophilic esophagitis (EoE) patients and promotes esophageal eosinophilia in mice, following an IL-13 challenge. However, the role of IL-13 has not been clearly investigated in allergen-induced EoE. Accordingly, we tested the hypothesis that IL-13 is required in allergen-induced EoE. Mice deficient in IL-13, STAT (signal transducer and activator of transcription)6 and both IL-4/IL-13 genes with their respective controls were challenged with Aspergillus extract, and IL-5 gene deficient with their control were challenged with recombinant IL-13, intranasally. The lung and esophageal eosinophils, mast cells and collagen accumulation were examined. Herein, we report that intranasal delivery of IL-13 promotes IL-5-dependent esophageal eosinophilia. However, allergen-induced EoE is not impaired in the IL-13 gene-deficient mice. In addition, wild-type and IL-13 gene-deficient mice demonstrated a comparable level of mast cells and collagen accumulation in the esophagus, following allergen-induced experimental EoE. Similarly, we found that esophageal eosinophilia in IL-4/IL-13 double gene-deficient and STAT6 gene-deficient mice were also not reduced following allergen-induced experimental EoE. In contrast, lung eosinophilia was significantly reduced in mice deficient in IL-13, both IL-4/IL-13 and STAT6 genes following allergen challenge. In conclusion, our data establish that allergen-induced EoE pathogenesis is independent of IL-13, whereas IL-13 is required for allergen-induced lung eosinophilia.
AuthorsRituraj Niranjan, Madhavi Rayapudi, Akanksha Mishra, Parmesh Dutt, Scott Dynda, Anil Mishra
JournalImmunology and cell biology (Immunol Cell Biol) Vol. 91 Issue 6 Pg. 408-15 (Jul 2013) ISSN: 1440-1711 [Electronic] United States
PMID23689305 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Allergens
  • Antigens, Fungal
  • Interleukin-13
  • Interleukin-5
  • STAT6 Transcription Factor
  • Interleukin-4
  • Collagen
Topics
  • Administration, Intranasal
  • Allergens (immunology)
  • Animals
  • Antigens, Fungal (immunology)
  • Aspergillus (immunology, metabolism)
  • Cell Movement (immunology)
  • Collagen (metabolism)
  • Eosinophilic Esophagitis (immunology)
  • Eosinophils (immunology)
  • Esophagus (immunology)
  • Humans
  • Interleukin-13 (genetics, immunology, metabolism)
  • Interleukin-4 (genetics)
  • Interleukin-5 (genetics)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • STAT6 Transcription Factor (genetics)

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