Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Macrophage polarization represents a fundamental plasticity process within innate immunity, profoundly influencing tissue homeostasis and disease progression. Based on developmental origins, macrophages are categorized into tissue-resident macrophages and monocyte-derived macrophages, which collectively form a dynamic host defense network. Notably, the functional states of macrophages exist along a continuum, extending beyond the classical pro-inflammatory (M1) and anti-inflammatory/reparative (M2) dichotomy. These states are dynamically shaped by spatiotemporally heterogeneous microenvironmental signals and coordinated through intricate molecular networks. Key signaling pathways guide polarization directions. Metabolic reprogramming, where M1 polarization relies on glycolysis and the pentose phosphate pathway while M2 polarization favors oxidative phosphorylation and fatty acid oxidation, not only supplies energy but also generates regulatory metabolites. Furthermore, epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, contribute to stabilizing polarized phenotypes. These mechanisms are interconnected, forming feedback loops that collectively sculpt macrophage functional diversity. Dysregulated polarization underlies numerous diseases. In response, therapeutic strategies targeting macrophage polarization are rapidly emerging. These inc

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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