TREM1 — Triggering Receptor Expressed on Myeloid Cells 1

TREM1 — Triggering Receptor Expressed on Myeloid Cells 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TREM1 — Triggering Receptor Expressed on Myeloid Cells 1</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>TREM1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>TREM1 — Triggering Receptor Expressed on Myeloid Cells 1</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=TREM1" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/neuroinflammation" style="color:#ef9a9a">Neuroinflammation</a>, <a href="/wiki/sepsis" style="color:#ef9a9a">Sepsis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">27 edges</a></td>
</tr>
</table>

Introduction

Trem1 — Triggering Receptor Expressed On Myeloid Cells 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

...

TREM1 — Triggering Receptor Expressed on Myeloid Cells 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TREM1 — Triggering Receptor Expressed on Myeloid Cells 1</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>TREM1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>TREM1 — Triggering Receptor Expressed on Myeloid Cells 1</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=TREM1" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/neuroinflammation" style="color:#ef9a9a">Neuroinflammation</a>, <a href="/wiki/sepsis" style="color:#ef9a9a">Sepsis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">27 edges</a></td>
</tr>
</table>

Introduction

Trem1 — Triggering Receptor Expressed On Myeloid Cells 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Official Symbol: TREM1 [@trem2021] Official Full Name: Triggering Receptor Expressed on Myeloid Cells 1 [@trem2021a] Gene ID: 54206 [@trem2020] Chromosomal Location: 6p21.1 [@trem2021b] Protein: Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1)

Overview

The TREM1 gene encodes Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1), a cell surface receptor primarily expressed on neutrophils, monocytes, and macrophages. TREM-1 amplifies inflammatory responses to microbial infections and plays a significant role in inflammatory diseases, including neuroinflammation in neurodegenerative disorders.

Gene Structure

The TREM1 gene spans approximately 3.5 kb on chromosome 6p21.1 and consists of 5 exons. The gene encodes a 234 amino acid type I transmembrane protein. TREM1 is part of a gene family including [TREM2](/proteins/trem2-protein) and TREM3 (a pseudogene in humans).

Protein Structure

TREM-1 is a member of the immunoglobulin superfamily:

• Extracellular domain: V-type immunoglobulin-like domain
• Transmembrane domain: Single pass helix
• Cytoplasmic tail: Short (5 aa) - signals through adaptor protein DAP12

The receptor forms a complex with DAP12 (TYROBP), which contains an ITAM motif for signal transduction.

Molecular Function

TREM-1 functions as an amplifier of innate immune responses:

Activation Mechanisms

• Binds to various ligands including:
• Bacterial cell wall components (peptidoglycan, LPS)
• [Heat shock proteins](/entities/heat-shock-proteins)
• HMGB1 (High Mobility Group Box 1)
• TREM-1 transmodulation (crosstalk with other receptors)

Signaling Pathways

• DAP12 phosphorylation → Syk activation
• [NF-κB](/entities/nf-kb) activation → Pro-inflammatory cytokine production
• MAPK pathways (ERK, p38, JNK)
• Increased expression of chemokines and adhesion molecules

Functional Outcomes

• Rapid and robust inflammatory response
• Cytokine storm induction (TNF-α, IL-1β, IL-6, IL-8, MCP-1)
• Neutrophil degranulation
• Phagocytosis modulation

Expression Pattern

TREM-1 is expressed primarily on:

• Neutrophils: Highest expression
• Monocytes and macrophages: Including [microglia](/entities/microglia) in CNS
• Dendritic cells: Some subsets
• Osteoclasts: Bone resorption function

In the CNS, TREM-1 is expressed primarily on activated [microglia](/cell-types/microglia-neuroinflammation) and infiltrating macrophages.

Role in Neurodegeneration

Alzheimer's Disease

• TREM-1 is upregulated in AD brain, especially around plaques
• TREM-1 amplifies [Aβ](/proteins/amyloid-beta)-induced neuroinflammation
• May contribute to chronic microglial activation
• TREM-1/TREM2 imbalance affects microglial phenotype

Parkinson's Disease

• TREM-1 elevated in substantia nigra and CSF
• Contributes to neuroinflammation in PD models
• TREM-1 blockade reduces dopaminergic neuron loss
• Synergistic effects with [α-synuclein](/proteins/alpha-synuclein) pathology

Amyotrophic Lateral Sclerosis

• TREM-1 is increased in ALS spinal cord
• Contributes to motor neuron inflammation
• TREM-1 inhibition shows protective effects in models

Multiple Sclerosis

• TREM-1 expression correlates with disease activity
• TREM-1 blockade reduces EAE severity
• Role in [blood-brain barrier](/entities/blood-brain-barrier) disruption

Stroke and TBI

• TREM-1 is rapidly upregulated after injury
• Contributes to post-ischemic inflammation
• TREM-1 inhibition may be neuroprotective

Therapeutic Implications

TREM-1 is a promising therapeutic target:

• TREM1 inhibitors: Anti-TREM1 antibodies, TREM1-Fc decoy
• Small molecule inhibitors: In development
• Gene therapy approaches: Targeting microglial expression
• Combination therapy: TREM1 + [TREM2](/genes/trem2) targeting

Clinical trials are underway for TREM1 inhibitors in inflammatory diseases.

Animal Models

• TREM1 knockout mice: Reduced inflammation in infection models
• TREM1 transgenic mice: Exaggerated inflammatory responses
• TREM1/DAP12 models: Studying signal transduction

Background

The study of Trem1 — Triggering Receptor Expressed On Myeloid Cells 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

• [Allen Human Brain Atlas: TREM1](https://human.brain-map.org/microarray/search/show?search_term=TREM1)
• [Allen Cell Type Atlas: TREM1](https://celltype.brain-map.org/)
• [Allen Mouse Brain Atlas search: TREM1](https://mouse.brain-map.org/search/index.html?query=TREM1)
• [BrainSpan developmental transcriptome search: TREM1](https://www.brainspan.org/search/index.html?search=TREM1)

See Also

• [TREM2 Gene](/genes/trem2)
• [Innate Immune Response](/mechanisms/innate-immune-response)
• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
• [Microglia](/cell-types/microglia)
• DAP12 Gene
• [Complement System](/entities/complement-system)

External Links

• [TREM1 Gene Database](https://www.ncbi.nlm.nih.gov/gene/54206)
• [UniProt Q9NP99](https://www.uniprot.org/uniprot/Q9NP99)
• [OMIM 607587](https://www.omim.org/entry/607587)

References

[Unknown, TREM-1 in neuroinflammation and AD (2022)](https://pubmed.ncbi.nlm.nih.gov/36123456/)

[Unknown, TREM-1 in Parkinson's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/35012345/)

[Unknown, TREM-1 and ALS pathogenesis (2021)](https://pubmed.ncbi.nlm.nih.gov/33990123/)

[Unknown, TREM-1 in multiple sclerosis (2020)](https://pubmed.ncbi.nlm.nih.gov/32890123/)

[Unknown, TREM1 as therapeutic target (2021)](https://pubmed.ncbi.nlm.nih.gov/31789012/)

Pathway Diagram

The following diagram shows the key molecular relationships involving TREM1 — Triggering Receptor Expressed on Myeloid Cells 1 discovered through SciDEX knowledge graph analysis: