Macrophage polarization: the epigenetic point of view

Curr Opin Lipidol. 2014 Oct;25(5):367-73. doi: 10.1097/MOL.0000000000000109.


Purpose of review: The first functions of macrophages to be identified by Metchnikoff were phagocytosis and microbial killing. Although these are important features, macrophages are functionally very complex and involved in virtually all aspects of life, from immunity and host defense, to homeostasis, tissue repair and development. To accommodate for this, macrophages adopt a plethora of polarization states. Understanding their transcriptional regulation and phenotypic heterogeneity is vital because macrophages are critical in many diseases and have emerged as attractive targets for therapy. Here, we review how epigenetic mechanisms control macrophage polarization.

Recent findings: It is becoming increasingly clear that chromatin remodelling governs multiple aspects of macrophage differentiation, activation and polarization. In recent years, independent research groups highlighted the importance of epigenetic mechanisms to regulate enhancer activity. Moreover, distinct histone-modifying enzymes were identified that control macrophage activation and polarization.

Summary: We recap epigenetic features of distinct enhancers and describe the role of Jumonji domain-containing protein 3 (Jmjd3) and Hdac3 as crucial mediators of macrophage differentiation, activation and polarization. We hypothesize that epigenetic enzymes could serve as the link between environment, cellular metabolism and macrophage phenotype. To conclude, we propose epigenetic intervention as a future pharmacological target to modulate macrophage polarization and to treat inflammatory diseases such as atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Atherosclerosis / etiology
  • Atherosclerosis / genetics*
  • Cell Differentiation / genetics*
  • Cell Polarity / genetics
  • Epigenesis, Genetic*
  • Gene Expression Regulation
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Macrophage Activation / genetics*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Phagocytosis / genetics


  • Jumonji Domain-Containing Histone Demethylases
  • KDM6B protein, human
  • Histone Deacetylases
  • histone deacetylase 3