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.
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel; and.
Netali
0000-0001-6530-0387
N
Ben Baruch-Morgenstern
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
Melissa K
MK
Mingler
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
Emily
E
Stucke
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
John A
JA
Besse
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
Ting
T
Wen
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel; and.
Hadar
H
Reichman
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel; and arielm@post.tau.ac.il rothenberg@cchmc.org.
Ariel
0000-0003-1626-3019
A
Munitz
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 arielm@post.tau.ac.il rothenberg@cchmc.org.
Marc E
ME
Rothenberg
D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D057765:Eosinophilic Esophagitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D015854:Up-Regulation
D018793:Interleukin-13; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic