Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease-associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. Here, we report that TREM2 is a thyroid hormone-regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone and synthetic thyroid hormone agonists (thyromimetics). Our findings report the endocrine regulation of TREM2 by thyroid hormone, and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small-molecule therapeutic agents.

髓样细胞 2 (TREM2) 上表达的触发受体是巨噬细胞和小胶质细胞上的细胞表面受体，可感知和响应疾病相关信号以调节这些先天免疫细胞的表型。TREM2 信号通路与多种疾病有关，从中枢神经系统的神经变性到外周代谢疾病。在这里，我们报告TREM2是一种甲状腺激素调节基因，它在巨噬细胞和小胶质细胞中的表达受到甲状腺激素和合成甲状腺激素激动剂（拟甲状腺素）的刺激。我们的研究结果报告了甲状腺激素对TREM2的内分泌调节，并为使用口服活性小分子治疗剂对 TREM2 信号通路进行药物治疗提供了独特的机会。