PT  - JOURNAL ARTICLE
AU  - Zuo, Li
AU  - Fulkerson, Patricia C.
AU  - Finkelman, Fred D.
AU  - Mingler, Melissa
AU  - Fischetti, Christine A.
AU  - Blanchard, Carine
AU  - Rothenberg, Marc E.
TI  - IL-13 Induces Esophageal Remodeling and Gene Expression by an Eosinophil-Independent, IL-13Rα2–Inhibited Pathway
AID  - 10.4049/jimmunol.1000471
DP  - 2010 Jul 01
TA  - The Journal of Immunology
PG  - 660--669
VI  - 185
IP  - 1
4099  - http://www.jimmunol.org/content/185/1/660.short
4100  - http://www.jimmunol.org/content/185/1/660.full
SO  - J. Immunol.2010 Jul 01; 185
AB  - 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-13Rα2 deletion, indicating an inhibitory effect of IL-13Rα2. 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-13Rα2.