Cutting edge: TREM-2 attenuates macrophage activation
Cutting edge: TREM-2 attenuates macrophage activation
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DOI：
10.4049/jimmunol.177.6.3520
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Colonna, Marco
中科院分区：
文献类型：
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作者：
Turnbull, Isaiah R.;Gilfillan, Susan;Colonna, Marco
髓样细胞上表达的触发受体2（TREM-2）通过衔接子DAP 12递送细胞内信号以调节免疫系统内外的髓样细胞功能。TREM-2在免疫中的作用由于未能在体内检测到TREM-2蛋白的表达而变得模糊。在这项研究中，我们表明，TREM-2表达的巨噬细胞浸润的组织从循环和交替激活IL-4可以诱导TREM-2。TREM-2表达通过用IFN-γ的LPS使巨噬细胞成熟而消除。使用TREM-2（-/-）小鼠，我们发现TREM-2连接抑制巨噬细胞响应TLR配体LPS、酵母聚糖和CpG产生细胞因子。此外，我们发现TREM-2完全解释了先前由DAP 12（-/-）巨噬细胞报道的增加的细胞因子产生。总之，这些数据表明TREM-2在新分化的和交替活化的巨噬细胞上表达，并起到抑制巨噬细胞活化的作用。
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 junctions 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.