Functional diversity of disorder-specific macrophages involved in various diseases

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)

Macrophages are highly plastic immune cells that adopt diverse functional states in response to the local microenvironment. The traditional M1/M2 polarization model that has long been used to describe macrophage activation is insufficient to capture the full spectrum of macrophage diversity observed in vivo. Advances in single-cell RNA sequencing (scRNA-seq) have revealed that macrophages exist in a continuum of transcriptional states formed by tissue-specific and disorder-specific cues. This insight has led to the recognition of disorder-specific macrophages, defined as macrophage subpopulations that emerge in response to pathological stimuli and play unique roles in disease progression. These macrophages exhibit distinct transcriptional signatures, epigenetic modifications, and functional properties shaped by their ontogeny and microenvironmental signals, arising from the reprogramming of resident macrophages or the differentiation of bone marrow-derived progenitors. Notable examples include macrophages in chronic infections (e.g., tuberculosis), immunosuppressive tumor-associated macrophages, lipid-associated macrophages in obesity, and disease-associated microglia in neurodegeneration. These subsets exhibit unique regulatory mechanisms, including enhancer remodeling driven by histone H3 lysine 27 acetylation in non-alcoholic steatohepatitis, CCAAT enhancer binding protein α

Evidence level

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

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