Details

Autor(en) / Beteiligte

• Ben Baruch-Morgenstern, Netali
• Mingler, Mellissa K.
• Stucke, Emily
• Besse, John A.
• Wen, Ting
• Reichman, Hadar
• Munitz, Ariel
• Rothenberg, Marc E.

Titel

Paired immunoglobulin-like receptor B inhibits IL-13–driven eosinophil accumulation and activation in the esophagus

Ist Teil von

• The Journal of immunology (1950), 2016-06, Vol.197 (3), p.707-714

Erscheinungsjahr

2016

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Eosinophilic esophagitis (EoE) is a T helper type 2 (Th2) cytokine–associated disease characterized by eosinophil infiltration, epithelial cell hyperplasia and tissue remodeling. Recent studies have highlighted a major contribution for IL-13 in EoE pathogenesis. Paired immunoglobulin-like receptor (PIR)-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 pro-fibrotic genes, genes promoting epithelial-to-mesenchymal transition (EMT) and genes associated with epithelial growth. These data identify PIR-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.