IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R alpha 2-inhibited pathway

J Immunol. 2010 Jul 1;185(1):660-9. doi: 10.4049/jimmunol.1000471. Epub 2010 Jun 11.


Eosinophilic esophagitis (EE) is an emerging disease associated with both food and respiratory allergy characterized by extensive esophageal tissue remodeling and abnormal esophageal gene expression, including increased IL-13. We investigated the ability of increased airway IL-13 to induce EE-like changes. Mice with pulmonary (but not esophageal) overexpression of IL-13 evidenced esophageal IL-13 accumulation and developed prominent esophageal remodeling with epithelial hyperplasia, angiogenesis, collagen deposition, and increased circumference. IL-13 induced notable changes in esophageal transcripts that overlapped with the human EE esophageal transcriptome. IL-13-induced esophageal eosinophilia was dependent on eotaxin-1 (but not eotaxin-2). However, remodeling occurred independent of eosinophils as demonstrated by eosinophil lineage-deficient, IL-13 transgenic mice. IL-13-induced remodeling was significantly enhanced by IL-13Ralpha2 deletion, indicating an inhibitory effect of IL-13Ralpha2. In the murine system, there was partial overlap between IL-13-induced genes in the lung and esophagus, yet the transcriptomes were divergent at the tissue level. In human esophagus, IL-13 levels correlated with the magnitude of the EE transcriptome. In conclusion, inducible airway expression of IL-13 results in a pattern of esophageal gene expression and extensive tissue remodeling that resembles human EE. Notably, we identified a pathway that induces EE-like changes and is IL-13-driven, eosinophil-independent, and suppressed by IL-13Ralpha2.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Eosinophilia / genetics
  • Eosinophilia / immunology*
  • Eosinophilia / pathology
  • Eosinophils / immunology*
  • Eosinophils / metabolism
  • Eosinophils / pathology
  • Esophagitis / genetics*
  • Esophagitis / immunology*
  • Esophagitis / pathology
  • Gene Expression Profiling
  • Humans
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / genetics
  • Interleukin-13 / physiology*
  • Interleukin-13 Receptor alpha2 Subunit / antagonists & inhibitors*
  • Interleukin-13 Receptor alpha2 Subunit / genetics
  • Interleukin-13 Receptor alpha2 Subunit / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Pulmonary Alveoli / immunology
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Up-Regulation / genetics
  • Up-Regulation / immunology


  • Interleukin-13
  • Interleukin-13 Receptor alpha2 Subunit