TREM2 Receptor in Alveolar Macrophages Promotes Lung Fibrosis: New Research Insights

Recent scientific studies have shed light on the role of the alveolar macrophage surface receptor TREM2 in the development of lung fibrosis, a chronic and progressive lung disease. Lung macrophages, essential immune cells present in the lung tissue, include tissue-resident macrophages from birth and monocyte-derived macrophages (Mo-AMs) that enter the lung in response to injury or infection.

In a groundbreaking study published in Nature Communications, researchers from the University of Alabama at Birmingham demonstrated that TREM2, a receptor protein expressed on Mo-AM cells, is a key regulator in the progression of lung fibrosis. The study found that TREM2 is highly expressed on these macrophages, especially in cases of idiopathic pulmonary fibrosis (IPF), and significantly contributes to the prolongation of macrophage survival, which in turn promotes fibrotic activity in the lungs.

The researchers revealed that TREM2 delays apoptosis (programmed cell death) of Mo-AMs, allowing these cells to survive longer in the lung environment. Lipid mediators present in lung surfactant, which normally prevent lung collapse, bind tightly with TREM2, further enhancing macrophage survival and activity. This pro-survival effect of TREM2 has the potential to exacerbate lung fibrosis.

Importantly, the study showed that blocking TREM2 — either through genetic deletion or using specific antibodies — can significantly reduce lung fibrosis in mouse models. Treatments that interfere with TREM2 binding to lipid mediators led to increased apoptosis of Mo-AMs and a decrease in fibrotic tissue development. Notably, these therapeutic interventions remained effective even when administered after fibrosis initiation.

The findings suggest that targeting TREM2 could be a promising strategy for developing new treatments against lung fibrosis, a disease characterized by stiffening of lung tissue that impairs breathing. The ability to attenuate fibrosis by disrupting macrophage survival mechanisms offers hope for future therapeutic options.

For more insight, the full study can be accessed in Nature Communications (2025). Source: https://medicalxpress.com/news/2025-07-alveolar-macrophage-cell-surface-receptor.html