Interaction of DAP12 and TREM2

TREM2 (triggering receptor expressed on myeloid cells 2 protein) is expressed on the cell membrane of a subset of myeloid cells - namely, immature dendritic cells, osteoclasts, tissue macrophages, and microglia. Like TREM1 the ligand for TREM2 is unknown. TREM2 signals through DAP12, leading to an increase in intracellular calcium and phosphorylation of ERK1/2 (Sharif & Knapp. 2008). It recognises anionic lipopolysacharides in the cell wall of bacteria and triggers the phagocytic uptake of bacteria and the release of reactive oxygen species (Neumann & Daly 2013). TREM2 on immature dendritic cells triggers upregulation of molecules involved in T cell co-stimulation such as CD86, CD40 and MHC class II, as well as up-regulation of the chemokine receptor CCR7 (Bouchon et al. 2001). In macrophages TREM2 is a negative regulator of inflammatory responses (Hamerman et al. 2006, Turnbull et al. 2006). From genome wide association studies, a TREM2 variant (encoding a substitution of arginine by histidine at residue 47 [R47H]) has been reported to be implicated in late-onset Alzheumer's disease (Neumann & Daly 2013).

TREM2（触发髓系细胞表达2蛋白）在特定髓系细胞亚群的细胞膜上表达，包括不成熟树突状细胞、破骨细胞、组织巨噬细胞和小胶质细胞。与TREM1类似，TREM2的配体尚不明确。TREM2通过DAP12进行信号传导，导致细胞内钙离子浓度增加以及ERK1/2磷酸化（Sharif & Knapp, 2008）。它能识别细菌细胞壁中的阴离子脂多糖，并触发细菌的吞噬摄取及活性氧的释放（Neumann & Daly, 2013）。不成熟树突状细胞上的TREM2可上调T细胞共刺激相关分子，如CD86、CD40和MHC II类分子，以及趋化因子受体CCR7的表达（Bouchon等，2001）。在巨噬细胞中，TREM2充当炎症反应的负调节因子（Hamerman等，2006；Turnbull等，2006）。基于全基因组关联研究，一种TREM2变异体（编码第47位精氨酸被组氨酸替代[R47H]）已被报道与阿尔茨海默病迟发性发病有关（Neumann & Daly, 2013）。