Cutting Edge: TREM-2 Attenuates Macrophage Activation

作者：Isaiah R. Turnbull, Susan Gilfillan, Marina Cella, Taiki Aoshi, Mark J. Miller, Laura Piccio, Maristela Hernandez, Marco Colonna · 发表于：The Journal of Immunology · 年份：2006 · DOI：10.4049/jimmunol.177.6.3520 · 被引用次数：735 · 研究领域：Inflammation biomarkers and pathways、Autoimmune and Inflammatory Disorders Research、Apelin-related biomedical research

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.