title: 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.
authors.affiliation: Division of Gastroenterology and Liver Disease, Digestive Health Institute, Case Western Reserve University, College of Medicine, Cleveland, OH 44106-5066, USA.
authors.forename: Rituraj
authors.initials: R
authors.lastname: Niranjan
authors.forename: Madhavi
authors.initials: M
authors.lastname: Rayapudi
authors.forename: Akanksha
authors.initials: A
authors.lastname: Mishra
authors.forename: Parmesh
authors.initials: P
authors.lastname: Dutt
authors.forename: Scott
authors.initials: S
authors.lastname: Dynda
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001230:Aspergillus / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D057765:Eosinophilic Esophagitis / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D004947:Esophagus / Q000276:immunology*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000235:genetics
chemical_list: D000485:Allergens; D000946:Antigens, Fungal; D018793:Interleukin-13; D015848:Interleukin-5; D050800:STAT6 Transcription Factor; D015847:Interleukin-4; D003094:Collagen