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TREMs in the immune system and beyond
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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“loss of function mutations in TREM2 (triggering receptor expressed on myeloid cells 2), which affect microglia phagocytosis and inflammation, are risk factors for ALS [425–427]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [426]
In the citing paper
“confirming the pivotal role played by microglia in ALS pathogenesis.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [426]
In the citing paper
“An important aspect of our BAC transgene design is the deletion of essential exons in three other TREM-like genes on the BAC, which are known to have important innate immunity function (Colonna, 2003; Ford and McVicar, 2009), and may play distinct roles in AD (Carrasquillo et al., 2017).”
From Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer’s Disease Models (2018) · cites this paper as Colonna, 2003
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Self-citationTREM-1 mediates interaction between substantia nigra microglia and peripheral neutrophils
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Metadata
- Authors
- Colonna, M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Colonna, Marco
- ORCID
- Colonna, Marco
- Venue
- Nature Reviews Immunology
- Published
- 2003-06-01
- Volume
- 3
- Issue
- 6
- Pages
- 445-453
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W1986899130
- Cited by
- 701
- References
- 84
- Citations by year
- 2026: 20 · 2025: 36 · 2024: 39 · 2023: 39 · 2022: 35 · 2021: 42 · 2020: 31 · 2019: 34 · 2018: 30 · 2017: 43 · 2016: 43 · 2015: 34 · 2014: 33 · 2013: 36 · 2012: 19
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Academy of Sciences of Ukraine
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TREM-1, TREM2, DAP12, myeloid cell activation, innate immunity, inflammation, dendritic cells, osteoclast development, TREM2 deficiency, bone cysts, demyelination, dementia
- MeSH terms
- Triggering Receptor Expressed on Myeloid Cells-1, Animals, Bone Cysts, Cell Differentiation, Dendritic Cells, Humans, Inflammation, Membrane Glycoproteins, Membrane Proteins, Phagocytes, Receptors, Immunologic, Signal Transduction, Cytokines, Chemokines, Hereditary Central Nervous System Demyelinating Diseases, Myeloid Cells, Adaptor Proteins, Signal Transducing
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