@article{fbcd44c2445946078fe3be953f5171da,
title = "TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor",
abstract = "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.",
keywords = "SARS-CoV-2, TREM2, innate immunity, neurodegeneration, therapeutics, thyroid hormone",
author = "Ferrara, {Skylar J.} and Priya Chaudhary and DeBell, {Margaret J.} and Gail Marracci and Hannah Miller and Evan Calkins and Edvinas Pocius and Napier, {Brooke A.} and Ben Emery and Dennis Bourdette and Scanlan, {Thomas S.}",
note = "Funding Information: 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. We would like to thank the Advanced Light Microscopy Core (supported by NIH P30 NS061800) at OHSU for technical assistance. S.J.F. and T.S.S. conceived of the project and experiments. S.J.F. and H.M. performed cell culture experiments and qRT-PCR. S.J.F. performed the phagocytosis assay and associated immunocytochemistry and microscopy. G.M. E.P. E.C. and P.C. conducted the EAE experiment and tissue procurement. S.J.F. and M.J.D. stained spinal cords and performed the associated microscopy and data analysis. S.J.F. synthesized the relevant compounds and performed overall data analysis. B.E. B.A.N. and D.B. provided advice on experimental design. S.J.F. and T.S.S. wrote the manuscript with input from P.C. B.E. B.A.N. and D.B. 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. Funding Information: 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. We would like to thank the Advanced Light Microscopy Core (supported by NIH P30 NS061800 ) at OHSU for technical assistance. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
year = "2022",
month = feb,
day = "17",
doi = "10.1016/j.chembiol.2021.07.014",
language = "English (US)",
volume = "29",
pages = "239--248.e4",
journal = "Cell Chemical Biology",
issn = "2451-9448",
publisher = "Elsevier Inc.",
number = "2",
}