Myeloid-lineage cells accomplish a myriad of homeostatic tasks including the recognition of pathogens, regulation of the inflammatory milieu, and mediation of tissue repair and regeneration. The innate immune receptor and its adaptor protein—triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12)—possess the ability to modulate critical cellular functions via crosstalk with diverse signaling pathways. As such, mutations in TREM2 and DAP12 have been found to be associated with a range of disease phenotypes. In particular, mutations in TREM2 increase the risk for Alzheimer's disease and other neurodegenerative disorders. The leading hypothesis is that microglia, the resident immune cells of the central nervous system, are the major myeloid cells affected by dysregulated TREM2-DAP12 function. Here, we review how impaired signaling by the TREM2-DAP12 pathway leads to altered immune responses in phagocytosis, cytokine production, and microglial proliferation and survival, thus contributing to disease pathogenesis.

中文翻译：

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TREM2在中枢神经系统稳态和神经退行性疾病中。

髓系谱系细胞完成了许多稳态工作，包括识别病原体，调节炎症环境以及介导组织修复和再生。先天性免疫受体及其衔接蛋白-在髓样细胞2（TREM2）上表达的触发受体和12 kDa的DNAX激活蛋白（DAP12）-具有通过多种信号通路通过串扰调节关键细胞功能的能力。这样，已经发现TREM2和DAP12中的突变与一系列疾病表型有关。特别是，TREM2突变会增加患阿尔茨海默氏病和其他神经退行性疾病的风险。主要假设是小胶质细胞是中枢神经系统的固有免疫细胞，是受TREM2-DAP12功能失调影响的主要髓样细胞。这里，