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.

• Authors: Netali Ben Baruch-Morgenstern, Melissa K Mingler, Emily Stucke, John A Besse, Ting Wen, Hadar Reichman, Ariel Munitz, Marc E Rothenberg
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 197 Issue 3 Pg. 707-14 (08 01 2016) ISSN: 1550-6606 [Electronic] United States
• PMID: 27324131 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by The American Association of Immunologists, Inc.

Chemical References

• Interleukin-13
• Pirb protein, mouse
• Receptors, Immunologic

Topics

• Animals
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Eosinophilic Esophagitis (immunology, metabolism, pathology)
• Eosinophils (metabolism, pathology)
• Flow Cytometry
• Immunohistochemistry
• Interleukin-13 (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oligonucleotide Array Sequence Analysis
• Real-Time Polymerase Chain Reaction
• Receptors, Immunologic (biosynthesis)
• Up-Regulation