Cutting Edge: Inhibition of Tlr and Fcr Responses in Macrophages by Triggering Receptor Expressed on Myeloid Cells (Trem)-2 and Dap12.
From: Department of Microbiology and Immunology, University of California-San Francisco, 514 Parnassus Avenue, San Francisco, CA 94143, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Aug 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 4
- Pages: 2051-5
- Medium: Print
- Language: English
- Citation (JAMA): Hamerman Jessica A, Jarjoura Jessica R, Humphrey Mary Beth, et al. Cutting Edge: Inhibition of Tlr and Fcr Responses in Macrophages by Triggering Receptor Expressed on Myeloid Cells (Trem)-2 and Dap12.. J. Immunol. Aug 2006;177:2051-5
Abstract
DAP12 is an ITAM-containing adapter that associates with receptors in myeloid and NK cells. DAP12-associated receptors can give activation signals leading to cytokine production; however, in some situations, DAP12 inhibits cytokine production stimulated through TLRs and FcRs. Here we show that Triggering Receptor Expressed on Myeloid cells (TREM)-2 is responsible for the DAP12-mediated inhibition in mouse macrophages. A chimeric receptor composed of the extracellular domain of TREM-2 and the cytoplasmic domain of DAP12 inhibited the TLR- and FcR-induced TNF production of DAP12-deficient macrophages, whereas a TREM-1 chimera did not. In wild-type macrophages, TREM-2 knockdown increased TLR-induced TNF production. A TREM-2 Fc fusion protein bound to macrophages, indicating that macrophages express a TREM-2 ligand. Thus, the interaction of TREM-2 and its ligand results in an inhibitory signal that can reduce the inflammatory response.
Mesh Headings (Keywords): Adaptor Proteins, Signal Transducing, Animals, Cells, Cultured, Inflammation Mediators, Ligands, Macrophages, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Fc, Receptors, Immunologic, Toll-Like Receptors, Tumor Necrosis Factor-alpha
Check for Full Text / PubMed Unique Identifier (PMID): 16887962
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