Macrophage polarization refers to development of a specific phenotype important for tissue homeostasis or host defense in response to environmental cues. Environmental factors that induce macrophage polarization include cytokines and microbial factors produced by pathogens or commensal microbiota. Signaling pathways utilized by these polarizing factors have been well characterized, but it is less clear how signals are converted into complex and sustained patterns of gene expression, and how macrophages are reprogrammed during polarization to alter their responses to subsequent environmental challenges. Emerging evidence, reviewed here, suggests an important role for epigenetic mechanisms in modulating and transmitting signals during macrophage polarization and reprogramming. Deeper understanding of epigenetic regulation of macrophage phenotype will enable development of gene-specific therapeutic approaches to enhance host defense while preserving tissue integrity and preventing chronic inflammatory diseases.
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