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-Il13Tg mice) and is overexpressed by esophageal eosinophils. CC10-Il13Tg/Pirb2/2 mice displayed increased esophageal eosinophilia and EoE pathology, including epithelial cell thickening, fibrosis, and angiogenesis, compared with CC10-Il13Tg/Pirb+/+ mice. Transcriptome analysis of primary Pirb+/+ and Pirb2/2 esophageal eosinophils revealed increased expression of transcripts associated with promoting tissue remodeling in Pirb2/2 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.