New review highlights TREM-1 receptor as target for inflammatory diseases

A comprehensive review recently published in Current Molecular Pharmacology consolidates the growing evidence surrounding the Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) as a central amplifier of innate immune responses and a promising therapeutic target for a range of inflammatory diseases.

The review, led by Eman R. Al Sawy and colleagues from Cairo University and E-JUST University in Egypt, provides an updated overview of TREM-1 biology, its complex signalling pathways, and its pathogenic roles in acute systemic inflammation, such as sepsis, as well as chronic conditions like inflammatory arthritis and neurodegenerative disorders, including Alzheimer's and Parkinson's diseases.

"Despite substantial advances in understanding inflammatory signalling pathways, current therapeutic strategies largely focus on inhibiting individual downstream cytokines, which has yielded limited success in complex inflammatory disorders," the authors note. They emphasize that a critical unmet need remains for approaches that target upstream amplification mechanisms.

The paper details how TREM-1, primarily expressed on myeloid cells, potentiates pro-inflammatory cytokine production and interacts with Toll-like receptors to amplify the immune response. While its soluble form (sTREM-1) shows promise as a prognostic biomarker for disease severity, particularly in sepsis, the translation of TREM-1-targeted therapies faces hurdles.

"Current evidence supports TREM-1 as a central amplifier of inflammation and a promising therapeutic target in sepsis, inflammatory arthritis, and neurodegenerative diseases," the corresponding author stated, "warranting further disease-specific translational investigation." The review critically discusses challenges including species-specific differences between animal models and humans, the risk of compromised protective immunity with non-selective inhibition, and the need for careful optimization of therapeutic timing and dosing.

While several antagonists like LR12 and LP17 have shown efficacy in preclinical models, and the inhibitor nanobiotide has reached clinical trials, the authors call for more research to define the optimal therapeutic window and identify patient subgroups most likely to benefit from TREM-1 modulation.