Mincle is an ITAM-coupled activating receptor that senses damaged cells
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- 7 September 2008
- journal article
- Published by Springer Nature in Nature Immunology
- Vol. 9 (10) , 1179-1188
- https://doi.org/10.1038/ni.1651
Abstract
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.Keywords
This publication has 52 references indexed in Scilit:
- The C-type Lectin Receptors CLEC-2 and Dectin-1, but Not DC-SIGN, Signal via a Novel YXXL-dependent Signaling CascadeJournal of Biological Chemistry, 2007
- Toll-like receptors in systemic autoimmune diseaseNature Reviews Immunology, 2006
- Plasmacytoid dendritic cell–specific receptor ILT7–FcεRIγ inhibits Toll-like receptor–induced interferon productionThe Journal of Experimental Medicine, 2006
- Neutrophils and immunity: challenges and opportunitiesNature Reviews Immunology, 2006
- Mechanistic basis of pre–T cell receptor–mediated autonomous signaling critical for thymocyte developmentNature Immunology, 2005
- The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascadesPhysiological Genomics, 2004
- Molecular identification of a danger signal that alerts the immune system to dying cellsNature, 2003
- High resolution mapping of an arthritis susceptibility locus on rat chromosome 4, and characterization of regulated phenotypesHuman Molecular Genetics, 2003
- Impaired IgG-Dependent Anaphylaxis and Arthus Reaction in FcγRIII (CD16) Deficient MiceImmunity, 1996
- Engineering galactose-binding activity into a C-type mannose-binding proteinNature, 1992