IL-33 Is Selectively Expressed By Esophageal Basal Layer Epithelial Cells during Allergic Inflammation
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Jared Travers, Mark Rochman, PhD, Ting Wen, PhD, Marc E. Rothenberg, MD PhD FAAAAI
Rationale: Recent studies on the pathogenesis of allergic disorders have focused on the involvement of innate cytokines produced by epithelial cells that promote the development of Th2 cell immunity. Herein, we focused on the involvement of the innate cytokine IL-33 in eosinophilic esophagitis (EoE). We aimed to test the hypothesis that IL-33 has increased expression in the epithelium in EoE.   

Methods: Quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC), immunofluorescence (IF), and flow cytometry were performed on esophageal biopsies of patients with inactive and active EoE or control individuals.

Results: IL-33 mRNA was increased (2-fold; p = 0.045) in active EoE biopsies compared to control biopsies. While IL-33 protein was not present in the esophageal epithelium in control individuals and in patients with inactive EoE, IL-33 protein was detected in the epithelium of patients with active EoE and was limited to the nuclei of the cellular layer in direct contact with the basement membrane between papillae. These IL-33-positive cells were characterized by low expression of podoplanin and p75 by both IF and flow cytometry. In contrast, IL-33-negative basal layer epithelial cells expressed high levels of podoplanin and p75. Further analysis revealed that the IL-33-positive cells co-express E-cadherin, keratin 5 and keratin 14, but not the proliferation marker Ki67.

Conclusions: IL-33 is selectively present only during active EoE disease in the most basal layer in a quiescent population. We propose that IL-33 is likely involved in disease pathogenesis.