Journal
GASTROENTEROLOGY
Volume 139, Issue 1, Pages 182-U286Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2010.03.057
Keywords
Esophagus; IL-15Ra; T Cells; EoE Patients
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Funding
- National Institutes of Health [R01 DK067255, R01 AI080581, AI45898, AI070235]
- Digestive Health Center [DK078392]
- Campaign Urging Research for Eosinophilic Disease (CURED)
- Food Allergy Project
- Buckeye Foundation
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BACKGROUND & AIMS: Quantitative microarray analyses have shown increased expression of interleukin-15 (IL-15) messenger RNA in the esophagus of patients with eosinophilic esophagitis (EoE), a recently recognized allergic disorder with poorly understood pathogenesis. METHODS: Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses were performed to examine protein and transcript levels in tissue samples from patients with EoE. Tissues from IL-15Ra-deficient and wild-type (control) mice were also examined. Tissue eosinophilia was determined by immunostaining for major basic protein and flow cytometry for cell-surface receptors. RESULTS: Quantitative polymerase chain reaction analyses showed that levels of IL-15 and its receptor IL-15Ra were increased similar to 6- and similar to 10-fold, respectively, in tissues from patients with EoE and similar to 3- and similar to 4-fold, respectively, in mice with allergen-induced EoE. A >2-fold increase in serum IL-15 protein levels was also detected in human EoE samples compared with those from healthy individuals. Human IL-15 messenger RNA levels correlated with esophageal eosinophilia (P < .001). IL-15Ra-deficient mice were protected from allergen-induced esophageal eosinophilia compared with controls (P < .001), even though similar levels of airway eosinophilia were observed in all mice. IL-15 activated STAT5 and CD4(+) T cells to produce cytokines that act on eosinophils. Incubation of primary esophageal epithelial cells from mice and humans with IL-15 caused a dose-dependent increase in the mRNA expression and protein levels of eotaxin-1, -2, and -3. CONCLUSIONS: IL-15 mediates in the pathogenesis of EoE. IL-15 activates CD4(+) T cells to produce cytokines that act on eosinophils.
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