This research was supported by NIH grants DK52798 (to T.S.S.) and GM133804 (to B.A.N.), and the National Multiple Sclerosis Society grants RG 5199A4 and RG-1607-25053 to D.B., RG 5106A1/1 and RG-2001-35775 to B.E., the Race to Erase MS to D.B., the OHSU Laura Fund for Innovation in Multiple Sclerosis to D.B. and T.S.S.
Cell Chemical Biology
Cellular control mechanisms, Medical bacteriology
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.
© 2021 Elsevier Ltd.
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Ferrara, S. J., Chaudhary, P., DeBell, M. J., Marracci, G., Miller, H., Calkins, E., Pocius, E., Napier, B. A., Emery, B., Bourdette, D., & Scanlan, T. S. (2021). TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor. Cell Chemical Biology, S2451945621003548. https://doi.org/10.1016/j.chembiol.2021.07.014