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


ABSTRACT: 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.

SUBMITTER: Ben Baruch-Morgenstern N 

PROVIDER: S-EPMC4955826 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Ben Baruch-Morgenstern Netali N   Mingler Melissa K MK   Stucke Emily E   Besse John A JA   Wen Ting T   Reichman Hadar H   Munitz Ariel A   Rothenberg Marc E ME  

Journal of immunology (Baltimore, Md. : 1950) 20160620 3


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-1  ...[more]

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