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Publication : TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells.

First Author  Ito H Year  2012
Journal  Eur J Immunol Volume  42
Issue  1 Pages  176-85
PubMed ID  21956652 Mgi Jnum  J:179836
Mgi Id  MGI:5304232 Doi  10.1002/eji.201141679
Citation  Ito H, et al. (2012) TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells. Eur J Immunol 42(1):176-85
abstractText  DCs play a key role in defense against infections and also in preventing inflammatory and autoimmune diseases. The response of DCs to pathogens is tightly regulated by many mechanisms to allow for appropriate, but not pathogenic, responses. We previously showed that DCs with deficiencies for two ITAM-bearing signaling adapters, DAP12 and FcRgamma, produce more inflammatory cytokines upon treatment with Toll-like receptor (TLR) agonists than WT DCs. Here, we investigated whether the TREM-2 receptor pairs with DAP12 to inhibit TLR responses in DCs. TREM-2-deficient BMDCs showed increased inflammatory cytokine and type I IFN production in response to TLR ligation. Additionally, TREM-2-deficient BMDCs had increased TLR-induced maturation and were more efficient at inducing antigen-specific T-cell proliferation upon CpG DNA stimulation compared with WT BMDCs. Finally, we showed that a TREM-2 ligand is expressed on the surface of BMDCs, suggesting that the TREM-2 receptor transduces inhibitory signals due to recognition of an endogenous ligand.
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