TY - JOUR
T1 - Paired ig-like receptor b inhibits il-13-driven eosinophil accumulation and activation in the esophagus
AU - Baruch-Morgenstern, Netali Ben
AU - Mingler, Melissa K.
AU - Stucke, Emily
AU - Besse, John A.
AU - Wen, Ting
AU - Reichman, Hadar
AU - Munitz, Ariel
AU - Rothenberg, Marc E.
N1 - Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84979608161&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1501873
DO - 10.4049/jimmunol.1501873
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AN - SCOPUS:84979608161
SN - 0022-1767
VL - 197
SP - 707
EP - 714
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -
