Cutting edge: TREM-2 attenuates macrophage activation

J Immunol. 2006 Sep 15;177(6):3520-4. doi: 10.4049/jimmunol.177.6.3520.

Abstract

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. The role of TREM-2 in immunity has been obscured by the failure to detect expression of the TREM-2 protein in vivo. 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. TREM-2 expression is abrogated by macrophage maturation with LPS of IFN-gamma. Using TREM-2(-/-) mice, we find that TREM-2 functions to inhibit cytokine production by macrophages in response to the TLR ligands LPS, zymosan, and CpG. Furthermore, we find that TREM-2 completely accounts for the increased cytokine production previously reported by DAP12(-/-) macrophages. Taken together, these data show that TREM-2 is expressed on newly differentiated and alternatively activated macrophages and functions to restrain macrophage activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Humans
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Jurkat Cells
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Macrophage Activation / immunology*
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism*
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Rats
  • Rats, Wistar
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Inflammation Mediators
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Immunologic
  • TYROBP protein, human
  • Trem2 protein, mouse