Mincle is an ITAM-coupled activating receptor that senses damaged cells.
Macrophage-inducible C-type lectin (Mincle) is expressed mainly in macrophages and is induced after exposure to various stimuli and stresses. Here we show that Mincle selectively associated with the Fc receptor common gamma-chain and activated macrophages to produce inflammatory cytokines and chemokines. Mincle-expressing cells were activated in the presence of dead cells, and we identified SAP130, a component of small nuclear ribonucloprotein, as a Mincle ligand that is released from dead cells. To investigate whether Mincle is required for normal responses to cell death in vivo, we induced thymocyte death by irradiating mice and found that transient infiltration of neutrophils into the thymus could be blocked by injection of Mincle-specific antibody. Our results suggest that Mincle is a receptor that senses nonhomeostatic cell death and thereby induces the production of inflammatory cytokines to drive the infiltration of neutrophils into damaged tissue.
Yamasaki
Sho
S
Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.
Ishikawa
Eri
E
Sakuma
Machie
M
Hara
Hiromitsu
H
Ogata
Koji
K
Saito
Takashi
T
D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death / Q000276:immunology*; D017124:Conserved Sequence; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020556:Neutrophil Infiltration / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D014161:Transduction, Genetic
C113583:Clecsf8 protein, mouse; D016207:Cytokines; D037181:Lectins, C-Type; D008565:Membrane Proteins; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D017411:Ribonucleoproteins, Small Nuclear