Department of Chemical Physiology and Biochemistry and Program in Chemical Biology, Oregon Health & Science University, L334, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
VA Portland Health Care System, Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
Cell Chem Biol. 2022 Feb 17;29(2):239-248.e4. doi: 10.1016/j.chembiol.2021.07.014. Epub 2021 Aug 9.
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.
髓系细胞触发受体 2（TREM2）是巨噬细胞和小胶质细胞表面的受体，可感知和响应与疾病相关的信号，从而调节这些先天免疫细胞的表型。TREM2 信号通路与从中枢神经系统的神经退行性变到外周代谢疾病等多种疾病有关。在这里，我们报告 TREM2 是甲状腺激素调节的基因，其在巨噬细胞和小胶质细胞中的表达受甲状腺激素和合成甲状腺激素激动剂（甲状腺激素模拟物）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靶向 TREM2 信号通路提供了独特的机会。
