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Gene Review

Trem2  -  triggering receptor expressed on myeloid...

Mus musculus

Synonyms: TREM-2, Trem2a, Trem2b, Trem2c, Triggering receptor expressed on monocytes 2, ...
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High impact information on Trem2

  • Knockdown of TREM2 in microglia inhibited phagocytosis of apoptotic neurons and increased gene transcription of tumor necrosis factor alpha and nitric oxide synthase-2, whereas overexpression of TREM2 increased phagocytosis and decreased microglial proinflammatory responses [1].
  • Here, we show expression of TREM2 in microglia [1].
  • Here we show that the triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12 [2].
  • Furthermore, we show that plexin-A1 associates with the triggering receptor expressed on myeloid cells-2 (Trem-2), linking semaphorin-signalling to the immuno-receptor tyrosine-based activation motif (ITAM)-bearing adaptor protein, DAP12 [3].
  • In this study, we show that TREM-2 is expressed on macrophages infiltrating the tissues from the circulation and that alternative activation with IL-4 can induce TREM-2 [4].

Biological context of Trem2


Anatomical context of Trem2

  • In addition, we identify microglial cells and oligodendrocytes as the major Dap12/Trem2-producing cells in the CNS and, consequently, as the predominant cell types involved in PLOSL pathogenesis [5].
  • These receptors associate with DAP12, and ligation of TREM-2 on the surface of macrophages leads to the release of nitric oxide [6].
  • Like TREM-1 and TREM-2, TREM-3 signals through DAP12, and when TREM-3 is transfected into an NK cell line it mediates redirected lysis [6].
  • The triggering receptor expressed on myeloid cells 2 (TREM-2) delivers intracellular signals through the adaptor DAP12 to regulate myeloid cell function both within and outside the immune system [4].
  • Brain regions with an incomplete blood-brain barrier had the lowest percentages of TREM-2- expressing microglia, whereas the lateral entorhinal and cingulate cortex had the highest percentages [7].

Associations of Trem2 with chemical compounds


Regulatory relationships of Trem2

  • Our studies define TREM-2 as a receptor family in mouse macrophages and demonstrate the capacity of these receptors to activate macrophage function through DAP12 [8].

Other interactions of Trem2

  • Thus, OSCAR but not TREM-2 is involved in the positive feedback loop of the immunoreceptor-NFATc1 pathway during osteoclastogenesis [9].

Analytical, diagnostic and therapeutic context of Trem2


  1. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. Takahashi, K., Rochford, C.D., Neumann, H. J. Exp. Med. (2005) [Pubmed]
  2. A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. Bouchon, A., Hernández-Munain, C., Cella, M., Colonna, M. J. Exp. Med. (2001) [Pubmed]
  3. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Takegahara, N., Takamatsu, H., Toyofuku, T., Tsujimura, T., Okuno, T., Yukawa, K., Mizui, M., Yamamoto, M., Prasad, D.V., Suzuki, K., Ishii, M., Terai, K., Moriya, M., Nakatsuji, Y., Sakoda, S., Sato, S., Akira, S., Takeda, K., Inui, M., Takai, T., Ikawa, M., Okabe, M., Kumanogoh, A., Kikutani, H. Nat. Cell Biol. (2006) [Pubmed]
  4. Cutting Edge: TREM-2 Attenuates Macrophage Activation. Turnbull, I.R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., Colonna, M. J. Immunol. (2006) [Pubmed]
  5. Dap12 and Trem2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. Kiialainen, A., Hovanes, K., Paloneva, J., Kopra, O., Peltonen, L. Neurobiol. Dis. (2005) [Pubmed]
  6. Characterization of TREM-3, an activating receptor on mouse macrophages: definition of a family of single Ig domain receptors on mouse chromosome 17. Chung, D.H., Seaman, W.E., Daws, M.R. Eur. J. Immunol. (2002) [Pubmed]
  7. Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. Schmid, C.D., Sautkulis, L.N., Danielson, P.E., Cooper, J., Hasel, K.W., Hilbush, B.S., Sutcliffe, J.G., Carson, M.J. J. Neurochem. (2002) [Pubmed]
  8. Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family. Daws, M.R., Lanier, L.L., Seaman, W.E., Ryan, J.C. Eur. J. Immunol. (2001) [Pubmed]
  9. Contribution of nuclear factor of activated T cells c1 to the transcriptional control of immunoreceptor osteoclast-associated receptor but not triggering receptor expressed by myeloid cells-2 during osteoclastogenesis. Kim, Y., Sato, K., Asagiri, M., Morita, I., Soma, K., Takayanagi, H. J. Biol. Chem. (2005) [Pubmed]
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