TREMs in the immune system and beyond

Nat Rev Immunol. 2003 Jun;3(6):445-53. doi: 10.1038/nri1106.


Triggering receptors expressed by myeloid cells (TREMs) belong to a rapidly expanding family of receptors that include activating and inhibitory isoforms encoded by a gene cluster linked to the MHC. TREM1 and TREM2 activate myeloid cells by signalling through the adaptor protein DAP12. TREM1 triggers phagocyte secretion of pro-inflammatory chemokines and cytokines, amplifying the inflammation that is induced by bacteria and fungi. TREM2 activates monocyte-derived dendritic cells and regulates osteoclast development. Remarkably, TREM2 deficiency leads to a severe disease that is characterized by bone cysts and demyelination of the central nervous system, which results in dementia, implying that the function of TREM2 extends beyond the immune system.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Bone Cysts / etiology
  • Cell Differentiation
  • Chemokines / biosynthesis
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology
  • Hereditary Central Nervous System Demyelinating Diseases / etiology
  • Humans
  • Inflammation / immunology
  • Membrane Glycoproteins / immunology*
  • Membrane Proteins
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology*
  • Phagocytes / immunology
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / physiology
  • Signal Transduction
  • Triggering Receptor Expressed on Myeloid Cells-1


  • Adaptor Proteins, Signal Transducing
  • Chemokines
  • Cytokines
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Immunologic
  • TREM1 protein, human
  • TREM2 protein, human
  • TYROBP protein, human
  • Triggering Receptor Expressed on Myeloid Cells-1