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

Skylar J. Ferrara, Priya Chaudhary, Margaret J. DeBell, Gail Marracci, Hannah Miller, Evan Calkins, Edvinas Pocius, Brooke A. Napier, Ben Emery, Dennis Bourdette, Thomas S. Scanlan

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)239-248.e4
JournalCell Chemical Biology
Volume29
Issue number2
DOIs
StatePublished - Feb 17 2022

Keywords

  • SARS-CoV-2
  • TREM2
  • innate immunity
  • neurodegeneration
  • therapeutics
  • thyroid hormone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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