Mincle is an ITAM-coupled activating receptor that senses damaged cells
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.
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Dying cells expose or release an unidentified DAMP recognized by CLEC9A on CD8α+ DC, which activates Syk kinase and cross-presentation of associated antigens on MHC class I.
“Dying cells also expose or release another as yet unidentified DAMP which is recognized by a receptor, CLEC9A, present on CD8α+ DC 55. This activates Syk kinase and cross-presentation of associated antigens on class I MHC.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [55]
CLRs can sense necrotic cell death.
“Although their primary importance is in host defence against pathogens, CLRs can sense necrotic cell death72.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [72]
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References 53 · Cited by 740
- Authors
- Yamasaki, S., Ishikawa, E., Sakuma, M., Hara, H., Ogata, K., & Saito, T.
- Affiliations
- RIKEN (JP)
- Saga University (JP)
- Hospital for Sick Children (CA)
- Corresponding author
- Yamasaki, Sho
- Saito, Takashi
- Venue
- Nature Immunology
- Published
- 2008-09-07
- Volume
- 9
- Issue
- 10
- Pages
- 1179-1188
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2065429310
- Cited by
- 740
- References
- 53
- Citations by year
- 2026: 30 · 2025: 29 · 2024: 36 · 2023: 33 · 2022: 44 · 2021: 43 · 2020: 45 · 2019: 38 · 2018: 45 · 2017: 50 · 2016: 54 · 2015: 35 · 2014: 42 · 2013: 43 · 2012: 42
- FWCI
- 18.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- Mincle, SAP130, C-type lectin receptors, macrophages, dead cell clearance, inflammatory cytokines, chemokines, neutrophil infiltration, thymocyte death, innate immunity, small nuclear ribonucleoproteins
- MeSH terms
- Amino Acid Sequence, Animals, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Macrophage Activation, Macrophages, Membrane Proteins, Mice, Inbred C57BL, Models, Molecular, Molecular Sequence Data, Receptors, Immunologic, Transduction, Genetic, Immunoblotting, Cytokines, Cell Death, Conserved Sequence, Ribonucleoproteins, Small Nuclear, Receptors, IgG, Epitope Mapping, Reverse Transcriptase Polymerase Chain Reaction, Neutrophil Infiltration, Lectins, C-Type, Immunoprecipitation, Mice
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