Cutting edge: Inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12
Cutting edge: Inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12
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DOI：
10.4049/jimmunol.177.4.2051
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发表时间：
2006-08-15
影响因子：
4.4
通讯作者：
Lanier, Lewis L.
中科院分区：
文献类型：
--
作者：
Hamerman, Jessica A.;Jarjoura, Vessica R.;Lanier, Lewis L.
DAP 12是一种含有ITAM的衔接子，与骨髓和NK细胞中的受体相关。DAP 12相关受体可以提供导致细胞因子产生的激活信号;然而，在某些情况下，DAP 12抑制通过TLR和FcR刺激的细胞因子产生。在这里，我们表明，触发受体表达的髓样细胞（TREM）-2是负责DAP 12介导的抑制小鼠巨噬细胞。由TREM-2的细胞外结构域和DAP 12的细胞质结构域组成的嵌合受体抑制TLR和TcR诱导的DAP 12缺陷型巨噬细胞的TNF产生，而TREM-1嵌合体则没有。在野生型巨噬细胞中，TREM-2敲低增加TLR诱导的TNF产生。TREM-2 Fc融合蛋白与巨噬细胞结合，表明巨噬细胞表达TREM-2配体。因此，TREM-2与其配体的相互作用产生可降低炎症反应的抑制信号。
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 TcR-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.