Neutrophil infiltration during inflammation is regulated by PILR? via modulation of integrin activation.

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 (PILR?), 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 ?2 integrin ligand ICAM-1. PILR? expressed on neutrophils constitutively associated in cis with its ligands, resulting in clustering of PILR? during stimulation with a chemoattractant. Clustering of PILR? enhanced ITIM-mediated signaling, thus modulating ?2 integrin inside-out activation. These data demonstrate that neutrophil recruitment in inflammatory responses is regulated by PILR? via modulation of integrin activation. [ABSTRACT FROM AUTHOR]

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