Paired Ig-like Receptor B Inhibits IL-13–Driven Eosinophil Accumulation and Activation in the Esophagus

Eosinophilic esophagitis (EoE) is a Th2 cytokine–associated disease characterized by eosinophil infiltration, epithelial cell hyperplasia, and tissue remodeling. Recent studies highlighted a major contribution for IL-13 in EoE pathogenesis. Paired Ig-like receptor B is a cell surface immune-inhibitory receptor that is expressed by eosinophils and postulated to regulate eosinophil development and migration. We report that Pirb is upregulated in the esophagus after inducible overexpression of IL-13 (CC10- Il13 Tg mice) and is overexpressed by esophageal eosinophils. CC10- Il13 Tg / Pirb −/− mice displayed increased esophageal eosinophilia and EoE pathology, including epithelial cell thickening, fibrosis, and angiogenesis, compared with CC10- Il13 Tg / Pirb +/+ mice. Transcriptome analysis of primary Pirb +/+ and Pirb −/− esophageal eosinophils revealed increased expression of transcripts associated with promoting tissue remodeling in Pirb −/− eosinophils, including profibrotic genes, genes promoting epithelial-to-mesenchymal transition, and genes associated with epithelial growth. These data identify paired Ig-like receptor B as a molecular checkpoint in IL-13–induced eosinophil accumulation and activation, which may serve as a novel target for future therapy in EoE.