triggering receptor expressed on myeloid cells 2; triggering receptor expressed on monocytes 2 (TREM2)

Function

• possible role in chronic inflammatory conditions
• may stimulate production of constitutive rather than inflammatory chemokines & cytokines
• forms a receptor signaling complex with TYROBP (TYRO protein tyrosine kinase binding protein); activating immune responses in macrophages & dendritic cells
• associates with DAP12 for its signaling function
• LILRB2 mediates TREM2 signaling
  • RHOH & NCK2 encode signaling molecules downstream from TREM2 that influence cytoskeletal rearrangement of microglia
• has both exogenous ligands on pathogens & endogenous ligands
  • Hsp60 is appears to be an agonist of TREM2
  • an endogenous ligand may be present on dendritic cells
• activation of TREM2 may stimulate
  • proliferation of CD4-positive T-cells
  • secretion of TNF & CCL2
• TREM2 may have anti-inflammatory function(s) via inhibition of Toll-like receptor(s)
  • TREM2 can inhibit maturation of dendritic cells
  • TREM2 can inhibit type I interferon responses
  • TREM2 can inhibit induction of antigen-specific T-cell proliferation

Compartment

• isoform 1: cell membrane
• isoforms 2,3: secreted

Alternative splicing

named isoforms=3

Expression

• macrophages
• dendritic cells
• osteoclasts
• NOT found on granulocytes or monocytes
• expressed on myeloid cells in CSF & as soluble TREM2 in CSF
• in the CNS, expressed on microglia
  • expressed throughout the CNS, especially in white matter
  • strongest expression in the basal ganglia, corpus callosum, medulla oblongata & spinal cord
  • expression rises in parallel with expression of beta-amyloid in the cerebral cortex
  • TREM2 is overexpressed in subtype 1 (hyperplastic subtype) of Alzheimer's disease

Pathology

• CSF soluble TREM2 & TREM2 expressed on microglia may play a role in facilitation of PHF-tau propagation by activated microglia in association with beta-amyloid
• defects in TREM2 or TYROBP genes associated with presenile dementia with bone cysts

Polymorphism

• TREM2 variant rs75932628 confers a 3-fold increase in risk for Alzheimer's disease
  • increased risk attributed to diminished function of TREM2

More general terms

• triggering receptor expressed on myeloid cells

Additional terms

• polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), presenile dementia with bone cysts; Nasu-Hakola disease

Database

• OMIM: https://mirror.omim.org/entry/605086
• OMIM: https://mirror.omim.org/entry/221770
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=54209
• UniProt: http://www.uniprot.org/uniprot/Q9NZC2.html