Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12
| Autor: | Lewis L. Lanier, William E. Seaman, Jessica A. Hamerman, Jessica Jarjoura, Mary Beth Humphrey, Mary C. Nakamura |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Myeloid
medicine.medical_treatment Immunology Macrophage-activating factor Receptors Fc Ligands Mice Extracellular medicine Immunology and Allergy Animals Receptors Immunologic Receptor Cells Cultured Adaptor Proteins Signal Transducing Mice Knockout Membrane Glycoproteins Chemistry TREM2 Tumor Necrosis Factor-alpha Macrophages Toll-Like Receptors Signal transducing adaptor protein Cell biology Mice Inbred C57BL Interleukin 10 Cytokine medicine.anatomical_structure Inflammation Mediators |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 177(4) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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