Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses.
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Kiyotake R, Oh-Hora M, Ishikawa E, Miyamoto T, Ishibashi T, Yamasaki S
Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses.
J Biol Chem. 2015 Oct 16;290(42):25322-32. doi: 10.1074/jbc.M115.645234. Epub 2015 Aug 20.
- PubMed ID
- 26296894 [ View in PubMed]
- Abstract
C-type lectin receptors (CLRs) are an emerging family of pattern recognition receptors that recognizes pathogens or damaged tissue to trigger innate immune responses. However, endogenous ligands for CLRs are not fully understood. In this study, we sought to identify an endogenous ligand(s) for human macrophage-inducible C-type lectin (hMincle). A particular fraction of lipid extracts from liver selectively activated reporter cells expressing hMincle. MS analysis determined the chemical structure of the active component as cholesterol. Purified cholesterol in plate-coated and crystalized forms activates reporter cells expressing hMincle but not murine Mincle (mMincle). Cholesterol crystals are known to activate immune cells and induce inflammatory responses through lysosomal damage. However, direct innate immune receptors for cholesterol crystals have not been identified. Murine macrophages transfected with hMincle responded to cholesterol crystals by producing pro-inflammatory cytokines. Human dendritic cells expressed a set of inflammatory genes in response to cholesterol crystals, and this was inhibited by anti-human Mincle. Importantly, other related CLRs did not bind cholesterol crystals, whereas other steroids were not recognized by hMincle. These results suggest that cholesterol crystals are an endogenous ligand for hMincle and that they activate innate immune responses.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Cholesterol C-type lectin domain family 4 member E Protein Humans UnknownLigandDetails - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Cholesterol Approved Investigational AQP9 366 upregulated Cholesterol results in increased expression of AQP9 mRNA 15q21.3 Cholesterol Approved Investigational AREG 374 upregulated Cholesterol results in increased expression of AREG mRNA 4q13.3 Cholesterol Approved Investigational CCL1 6346 upregulated Cholesterol results in increased expression of CCL1 mRNA 17q12 Cholesterol Approved Investigational CCL4 6351 upregulated Cholesterol results in increased expression of CCL4 mRNA 17q12 Cholesterol Approved Investigational CLEC5A 23601 upregulated Cholesterol results in increased expression of CLEC5A mRNA 7q34 Cholesterol Approved Investigational CSF1 1435 upregulated Cholesterol results in increased expression of CSF1 mRNA 1p13.3 Cholesterol Approved Investigational DCSTAMP 81501 upregulated Cholesterol results in increased expression of DCSTAMP mRNA 8q22.3 Cholesterol Approved Investigational FLT1 2321 upregulated Cholesterol results in increased expression of FLT1 mRNA 13q12.3 Cholesterol Approved Investigational GP1BA 2811 upregulated Cholesterol results in increased expression of GP1BA mRNA 17p13.2 Cholesterol Approved Investigational HBEGF 1839 upregulated Cholesterol results in increased expression of HBEGF mRNA 5q31.3 Cholesterol Approved Investigational IL1B 3553 upregulated Cholesterol results in increased expression of IL1B mRNA 2q14.1 Cholesterol Approved Investigational IL1RN 3557 upregulated Cholesterol results in increased expression of IL1RN mRNA 2q14.1 Cholesterol Approved Investigational INHBA 3624 upregulated Cholesterol results in increased expression of INHBA mRNA 7p14.1 Cholesterol Approved Investigational KITLG 4254 upregulated Cholesterol results in increased expression of KITLG mRNA 12q21.32 Cholesterol Approved Investigational LPL 4023 upregulated Cholesterol results in increased expression of LPL mRNA 8p21.3 Cholesterol Approved Investigational OCSTAMP 128506 upregulated Cholesterol results in increased expression of OCSTAMP mRNA 20q13.12 Cholesterol Approved Investigational PSAT1 29968 upregulated Cholesterol results in increased expression of PSAT1 mRNA 9q21.2 Cholesterol Approved Investigational RGCC 28984 upregulated Cholesterol results in increased expression of RGCC mRNA 13q14.11 Cholesterol Approved Investigational SLC1A3 6507 upregulated Cholesterol results in increased expression of SLC1A3 mRNA 5p13.2 Cholesterol Approved Investigational SLC28A3 64078 upregulated Cholesterol results in increased expression of SLC28A3 mRNA 9q21.32-q21.33 Cholesterol Approved Investigational SLC7A5 8140 upregulated Cholesterol results in increased expression of SLC7A5 mRNA 16q24.2 Cholesterol Approved Investigational TIMP3 7078 upregulated Cholesterol results in increased expression of TIMP3 mRNA 22q12.3 Cholesterol Approved Investigational TM4SF19 116211 upregulated Cholesterol results in increased expression of TM4SF19 mRNA 3q29