TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor.

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.
Competing Interests: Declaration of interests The authors declare the following competing financial interest(s): S.J.F. and T.S.S. are inventors of licensed patent applications claiming central nervous system-penetrating prodrugs of nuclear receptor modulators and their uses, including drugs acting on the thyroid hormone receptors. T.S.S., D.B., and B.E. are co-founders of Autobahn Therapeutics, and T.S.S. is a Senior Advisor to Autobahn Therapeutics.
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