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Dysregulated Efferocytosis in CAD: TNF-α and TGF-β Silencing Reveals Functional Divergence in M1 and M2 Macrophages

Year: 2025

Type: article

Abstract: Efferocytosis, the process by which macrophages clear apoptotic cells, plays a vital role in maintaining immune homeostasis. This study explores the influence of inflammatory cytokines—tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β)—on efferocytosis dysregulation in coronary artery disease (CAD). Peripheral blood samples were collected from 27 non-obstructive and 29 obstructive CAD patients to isolate monocytes, which were then differentiated into M1 and M2 macrophages using specific cytokine stimuli. These macrophages were transfected with TNF-α and TGF-β siRNA to assess cytokine impact on efferocytosis. Expression levels of the efferocytosis receptor MERTK and its regulatory protease ADAM17 were quantified via qPCR. Statistical analysis revealed significantly higher MERTK expression in M2 macrophages compared to M1 (p = 0.002). Notably, TNF-α silencing enhanced efferocytosis in M2 macrophages, with increased clearance of early apoptotic bodies in non-obstructive CAD and late apoptotic bodies in obstructive CAD (both p < 0.001). These findings suggest that macrophage phenotype, apoptotic stage, and cytokine environment influence efferocytosis efficiency and may involve pathways beyond MERTK-ADAM17. They offer preliminary mechanistic insights into cytokine-mediated modulation of efferocytosis in CAD. Further in vivo studies are needed to confirm these observations and evaluate their relevance for future therapeutic strategies.

Source: Immuno

DOI: 10.3390/immuno6010006