Cutting edge: TREM-2 attenuates macrophage activation.
The triggering receptor expressed on myeloid cells 2 (TREM-2) delivers intracellular signals through the adaptor DAP12 to regulate myeloid cell function both within and outside the immune system. The role of TREM-2 in immunity has been obscured by the failure to detect expression of the TREM-2 protein in vivo. In this study, we show that TREM-2 is expressed on macrophages infiltrating the tissues from the circulation and that alternative activation with IL-4 can induce TREM-2. TREM-2 expression is abrogated by macrophage maturation with LPS of IFN-gamma. Using TREM-2(-/-) mice, we find that TREM-2 functions to inhibit cytokine production by macrophages in response to the TLR ligands LPS, zymosan, and CpG. Furthermore, we find that TREM-2 completely accounts for the increased cytokine production previously reported by DAP12(-/-) macrophages. Taken together, these data show that TREM-2 is expressed on newly differentiated and alternatively activated macrophages and functions to restrain macrophage activation.
Pubmed ID: 16951310 RIS Download
Adaptor Proteins, Signal Transducing | Animals | Cell Differentiation | Cell Movement | Humans | Inflammation Mediators | Jurkat Cells | Lung | Macrophage Activation | Macrophages, Peritoneal | Membrane Glycoproteins | Membrane Proteins | Mice | Mice, Inbred BALB C | Mice, Inbred C57BL | Mice, Knockout | Rats | Rats, Wistar | Receptors, Immunologic