Published in Current Molecular Pharmacology, a comprehensive review by Eman R. Al Sawy and colleagues from Cairo University consolidates evidence on the triggering receptor expressed on myeloid cells-1 (TREM-1) as a central amplifier of inflammatory responses. The authors explain that TREM-1, primarily expressed on macrophages, monocytes, and neutrophils, potently enhances innate immune signaling through its adaptor protein DAP12 and crosstalk with Toll-like receptors. "Dysregulated TREM-1 activation is increasingly implicated in both acute and chronic inflammatory conditions, yet effective targeted therapies remain limited," said corresponding author Nesrine S. El Sayed.
The review covers TREM-1's pathogenic role in sepsis, where elevated soluble TREM-1 correlates with mortality; in arthritis, where TREM-1 inhibition reduces joint inflammation; and in neurodegenerative diseases like Alzheimer's and Parkinson's, where microglial TREM-1 contributes to neuroinflammation. Several antagonists—including LR12, LP17, GF9, and the clinical-stage nanobiotide—have shown promise in preclinical models. However, the authors caution that species differences, disease heterogeneity, and risks of immunosuppression require careful optimization. They conclude that TREM-1-directed therapies hold translational potential, particularly for patients with sepsis, rheumatoid arthritis, gout, and Alzheimer's disease, and call for well-designed clinical trials to define therapeutic windows and identify responsive patient subgroups.
