The triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial innate immune receptor associated with a lethal form of early, progressive dementia, Nasu-Hakola disease, and with an increased risk of Alzheimer’s disease. Microglial defects in phagocytosis of toxic aggregates or apoptotic membranes were proposed to be at the origin of the pathological processes in the presence of Trem2 inactivating mutations. Here, we show that TREM2 is essential for microglia-mediated synaptic refinement during the early stages of brain development. The absence of Trem2 resulted in impaired synapse elimination, accompanied by enhanced excitatory neurotransmission and reduced long-range functional connectivity. Trem2^−/− mice displayed repetitive behavior and altered sociability. TREM2 protein levels were also negatively correlated with the severity of symptoms in humans affected by autism. These data unveil the role of TREM2 in neuronal circuit sculpting and provide the evidence for the receptor’s involvement in neurodevelopmental diseases.

髓样细胞2（TREM2）上表达的触发受体是一种小胶质先天免疫受体，与致死性早期进展性痴呆，纳苏-哈科拉病相关，并且患阿尔茨海默氏病的风险增加。有毒的聚集体或凋亡膜的吞噬作用中的小胶质细胞缺陷被认为是存在Trem2失活突变的病理过程的起点。在这里，我们显示TREM2对于大脑发育早期的小胶质细胞介导的突触细化至关重要。Trem2的缺失会导致突触消除功能受损，并伴有兴奋性神经传递增强和远距离功能连通性降低。Trem2 ^-/-小鼠表现出重复行为并改变了社交能力。TREM2蛋白水平也与自闭症患者的症状严重程度负相关。这些数据揭示了TREM2在神经元回路雕刻中的作用，并为受体参与神经发育疾病提供了证据。