TREM1

(Triggering Receptor Expressed on Myeloid cells 1) It is an immune receptor found predominantly on myeloid lineage cells such as monocytes, macrophages, and microglia. It acts as a powerful amplifier of inflammatory responses.

🔹 Structure and Expression Type: Cell surface receptor, part of the immunoglobulin superfamily.

Expressed on:

Monocytes/macrophages

Neutrophils

Microglia (especially in pathological states)

Usually low or absent at rest, but upregulated during infection, inflammation, or cancer.

⚙️ Function Acts via DAP12, an adaptor protein that transmits activating signals.

Amplifies TLR (Toll-like receptor)-mediated responses → enhances cytokine and chemokine release (e.g., TNF-α, IL-6, IL-1β).

In microglia, it promotes:

Proinflammatory plasticity

Phagocytic activity

Response to brain injury and tumors

🧠 TREM1 in Neurological Disease In glioblastoma (as shown in the PNAS 2025 paper):

Tumor-derived extracellular vesicles (EVs) deliver TREM1 or activate its signaling in microglia.

This reprograms microglia toward a tumor-supportive phenotype via the SYK–PDK–STAT3 pathway.

In Alzheimer’s disease, TREM1 has been linked to exacerbated inflammation and worse outcomes.

In stroke and brain injury, TREM1 contributes to secondary neuroinflammation.

💉 Therapeutic Target Potential TREM1 blockade reduces:

Inflammation in sepsis

Tumor progression in GBM (shown in animal models)

Inhibitors:

LP17 peptide (experimental)

TREM1-Fc decoy receptor

Small molecules under development

⚠️ Therapeutic targeting must balance immune suppression with retaining antimicrobial defense.

🧪 Pathways Downstream of TREM1 DAP12 → SYK → PDK1 → STAT3

Promotes:

Cell survival

Cytokine expression

Metabolic reprogramming