title: TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells.
abstract: 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 FcRγ, 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.
authors.affiliation: Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hamerman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000818:Animals; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; C498716:Trem2 protein, mouse; C484963:Tyrobp protein, mouse; D012313:RNA