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TREMs in the immune system and beyond

Nature Reviews Immunology volume 3, pages 445–453 (2003)Cite this article

Key Points

  • Myeloid-cell activation is controlled by many families of receptors, each including activating and inhibitory isoforms.

  • Triggering receptors expressed by myeloid cells (TREMs) are encoded by a gene cluster on human chromosome 6 and mouse chromosome 17.

  • TREM1 is associated with the DAP12 adaptor and amplifies granulocytic and monocytic inflammatory responses during bacteria and fungus infections.

  • Blocking TREM1 function reduces mortality in experimental models of sepsis.

  • TREM2 can associate with the DAP12 adaptor and activates monocyte-derived dendritic cells.

  • TREM2 promotes the differentiation of osteoclasts and glial cells from monocytic precursors.

  • Rare null mutations of TREM2 in humans cause Nasu-Hakola disease, an autosomic recessive disorder that is characterized by bone cysts and demyelination of the central nervous system, resulting in bone fractures and presenile dementia.

Abstract

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.

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Figure 1: Organization of the human and mouse TREM gene cluster.
Figure 2: Schematic presentation of the role of TREM1 in inflammatory responses.
Figure 3: TREM regulation of myeloid-cell differentiation.

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Acknowledgements

I would like to thank S. Gilfillan and W. Barchet for helpful comments.

Author information

Authors and Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, 63110, Missouri, USA

    Marco Colonna

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Related links

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DATABASES

LocusLink

CBL

CCL2

CCL3

CCL7

CCR7

CD1A

CD3ζ

CD16

CD40L

DAP12

GM-CSF

GRB2

H60

HMG1

ICAM1

IFN-γ

IL-1α

IL-1β

IL-4

IL-8

IL-10

JNK

MCSF

MICA

MICB

MIF

NF-κB

NKp44

PTK

SHP1

SIRP-β1

SYK

TGF-β

TNF

TRANCE

ZAP70

OMIM

Nasu-Hakola disease

FURTHER INFORMATION

LILR nomenclature web site

KIR nomenclature web site

Glossary

MICROGLIA

Bone-marrow-derived macrophage lineage cells that are present in the CNS.

CAECAL LIGATION AND PUNCTURE

An experimental model of polymicrobial sepsis that is induced by ligation and perforation of the caecum.

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Colonna, M. TREMs in the immune system and beyond. Nat Rev Immunol 3, 445–453 (2003). https://doi.org/10.1038/nri1106

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