TREM1 (Triggering Receptor Expressed on Myeloid Cells 1) is an immunomodulatory receptor belonging to the immunoglobulin superfamily, primarily expressed on myeloid cells like neutrophils, monocytes, and macrophages. It plays a critical role in amplifying inflammatory responses during infections or tissue damage. Upon activation by ligands such as bacterial components or host-derived molecules (e.g., HMGB1. PGLYRP1), TREM1 synergizes with Toll-like receptor (TLR) signaling through its adaptor protein DAP12. driving the release of pro-inflammatory cytokines (e.g., IL-8. TNF-α) and chemokines. This pathway enhances neutrophil recruitment and microbial clearance but can also contribute to hyperinflammation if dysregulated.
TREM1 is implicated in inflammatory diseases, including sepsis, rheumatoid arthritis, and atherosclerosis. In sepsis, elevated TREM1 expression correlates with disease severity, making it a therapeutic target. TREM1-targeting antibodies, either antagonistic or agonistic, have been explored to modulate immune responses. Antagonistic antibodies block TREM1-DAP12 interactions, suppressing excessive inflammation in preclinical models of sepsis or colitis. Conversely, agonistic antibodies might boost immune responses in immunocompromised states.
Additionally, soluble TREM1 (sTREM1) is studied as a biomarker for infections and inflammatory conditions. Recent research also links TREM1 to non-infectious pathologies, including cancer, where it may regulate tumor-associated macrophages. Despite promising preclinical data, clinical translation remains ongoing, with challenges in specificity and safety. TREM1 antibodies thus represent a dual tool for both therapeutic intervention and diagnostic applications in inflammation-driven diseases.