title: Neutrophil infiltration during inflammation is regulated by PILRα via modulation of integrin activation.
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 β(2) 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 β(2) integrin inside-out activation. These data demonstrate that neutrophil recruitment in inflammatory responses is regulated by PILRα via modulation of integrin activation.
authors.affiliation: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Ikuo
authors.initials: I
authors.lastname: Shiratori
authors.forename: Junji
authors.initials: J
authors.lastname: Uehori
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D016023:Integrins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011940:Receptor Aggregation / Q000187:drug effects / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology
chemical_list: D016023:Integrins; C548037:PILRalpha protein, mouse; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine