Crucial discovery in regulating dysregulated & overamplified inflammation

Crucial discovery in regulating dysregulated & overamplified inflammation

Nov 12, 2012

Under the leadership of WANG Jing , Researcher, and ARASE Hisashi , Professor, Research Institute for Microbial Diseases, Immunology Frontier Research Center, Osaka University, a group of researchers has discovered that PILR α regulated neurtophil infiltration during inflammation via modulation of integrin activation -- a first-in-the-world research result, a finding crucial to controlling and/or preventing dysregulated or overamplified inflammatory response.

Abstract

" Acute inflammatory responses are important in host defense, whereas dysregulated inflammation results in life-threatening complications. Here we found that paired immunoglobulin-like type 2 receptor alpha (PILRα), an inhibitory receptor containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs), negatively regulated neutrophil infiltration during inflammation. Pilra−/− mice had increased neutrophil recruitment to inflammatory sites and were highly susceptible to endotoxin shock. Pilra−/− neutrophils showed enhanced transmigration ability and increased adhesion to the β2 integrin ligand ICAM-1. PILRα expressed on neutrophils constitutively associated in cis with its ligands, resulting in clustering of PILRα during stimulation with a chemoattractant. Clustering of PILRα enhanced ITIM-mediated signaling, thus modulating β2 integrin inside-out activation. These data demonstrate that neutrophil recruitment in inflammatory responses is regulated by PILRα via modulation of integrin activation. "

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To learn more about this research, please read the full research report entitled " Neutrophil infiltration during inflammation is regulated by PILRα via modulation of integrin activation " at this page of the Nature Immunology website.

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