P1-009　Disrupting ceramide-LMIR3 interaction prevents bacterial sepsis by stimulating neutrophil recruitment

• Published in: Japanese Journal of Clinical Immunology Vol. 38; no. 4; p. 313a
• Main Authors: 奥村, 康, 北浦, 次郎, 伊沢, 久未, 北村, 和名, 磯部, 優理
• Format: Journal Article
• Language: Japanese
• Published: 日本臨床免疫学会 2015; The Japan Society for Clinical Immunology
• ISSN: 0911-4300; 1349-7413
• DOI: 10.2177/jsci.38.313a

  An inhibitory receptor LMIR3/CD300f is mainly expressed in myeloid cells, including mast cells and neutrophils. We have recently demonstrated that ceramide-LMIR3 binding inhibits IgE- and mast cell-dependent allergic responses. Sepsis remains a major clinical problem. Negative regulation of innate immunity is associated with sepsis progression. Here we identify the critical role of ceramide-LMIR3 binding in suppressing innate host responses. LMIR3−/− mice were protected against lethality after cecal ligation and puncture (CLP), a murine model of septic peritonitis. In the peritoneal cavity of CLP-operated LMIR3−/− mice, mast cells and recruited neutrophils released high levels of neutrophil chemoattractants, leading to enhanced recruitment of neutrophils that efficiently eliminated Escherichia coli. Ceramide-LMIR3 interaction suppressed such release from Escherichia coli-stimulated mast cells and neutrophils. Importantly, treatment with ceramide antibody or LMIR3-Fc, which disrupted the ceramide-LMIR3 interaction, prevented CLP-induced sepsis by profoundly stimulating neutrophil recruitment. Thus, LMIR3 is an attractive target for the treatment of sepsis.