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Neutrophil infiltration during inflammation is regulated by PILR-α via modulation of integrin activation (Hisashi ARASE in Nature Immunology)
Acute inflammatory responses are important in host defense, whereas dysregulated inflammation results in life-threatening complications.
The authors found that paired immunoglobulin-like type 2 receptor alpha (PILRα), an inhibitory receptor containing an immunoreceptor tyrosine-based inhibitory motif (ITIM), negatively regulated neutrophil infiltration during inflammation.
Pilra-/- mice had increased neutrophil recruitment to inflammatory sites and were highly susceptible to endotoxin shock. PILRα-/- neutrophils showed enhanced transmigration ability and increased adhesion to the 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.
Immunology Frontier Research Center (WPI-IFReC), Osaka University