CD24 and Siglec-10 selectively repress tissue damage-induced immune responses.
Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1, heat shock protein 70, and heat shock protein 90; negatively regulates their stimulatory activity; and inhibits nuclear factor kappaB (NF-kappaB) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.
Chen
Guo-Yun
GY
Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Tang
Jie
J
Zheng
Pan
P
Liu
Yang
Y
D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D024243:HMGB1 Protein / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D047468:Immunoprecipitation; D007249:Inflammation / Q000276:immunology*; D037102:Lectins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000276:immunology / Q000473:pathology; D051379:Mice; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000276:immunology; D017434:Protein Structure, Tertiary; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000276:immunology / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D016207:Cytokines; D024243:HMGB1 Protein; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D037102:Lectins; D008070:Lipopolysaccharides; D050505:Mutant Proteins; D011947:Receptors, Antigen, B-Cell; D011956:Receptors, Cell Surface; D051192:Receptors, Pattern Recognition; C426228:SIGLEC10 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; D051996:Transcription Factor RelA; D000082:Acetaminophen; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse