Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis

Eur J Immunol. 2007 May;37(5):1290-301. doi: 10.1002/eji.200636837.


Triggering receptor expressed on myeloid cells (TREM-2) is a membrane receptor associated with DAP12 that is expressed primarily in myeloid cells, including dendritic cells and microglia, and promotes fusion of osteoclast precursors into multinucleated cells. A rare autosomal recessive condition, Nasu-Hakola disease (NHD) is associated with loss-of-function mutations in DAP12 and TREM-2. The brain pathology observed in NHD patients suggests that disruption of the TREM-2/DAP12 pathway leads to neurodegeneration with demyelination and axonal loss. In this study, we have characterized TREM-2 protein expression on microglia using a newly produced monoclonal antibody directed against the mouse TREM-2 receptor. We report that TREM-2 expression is up-regulated in the spinal cord during both the early inflammatory and chronic phases of myelin oligodendrocyte glycoprotein (MOG)(35-55)peptide-induced experimental autoimmune encaphalomyelitis (EAE). We also demonstrate that TREM-2 is highly expressed on microglial cells in the central nervous system (CNS) during EAE and that blockade of TREM-2 during the effector phase of EAE results in disease exacerbation with more diffuse CNS inflammatory infiltrates and demyelination in the brain parenchyma. These results demonstrate a critical role for TREM-2 during inflammatory responses in the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Brain / immunology
  • Brain / metabolism
  • Brain / pathology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Fluorescent Antibody Technique
  • Macrophages / immunology
  • Macrophages / metabolism
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Microglia / metabolism
  • RNA, Messenger / analysis
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Up-Regulation


  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Immunologic
  • Trem2 protein, mouse