Macrophages provide a critical systemic network cells of the innate immune system. Emerging data suggest that in addition, they have important tissue-specific functions that range from clearance of surfactant from the lungs to neuronal pruning and establishment of gut homeostasis. The differentiation and tissue-specific activation of macrophages require precise regulation of gene expression, a process governed by epigenetic mechanisms such as DNA methylation, histone modification and chromatin structure. We argue that epigenetic regulation of macrophages is determined by lineage- and tissue-specific transcription factors controlled by the built-in programming of myeloid development in combination with signaling from the tissue environment. Perturbation of epigenetic mechanisms of tissue macrophage identity can affect normal macrophage tissue function and contribute to pathologies ranging from obesity and autoimmunity to neurodegenerative diseases.
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Supported by the European Research Council (309788 for the I.A. laboratory; 340345 for the S.J. laboratory), the I-CORE for chromatin and RNA regulation (I.A. laboratory), the Israel Science Foundation (703/15 for the I.A. laboratory; 887/11 for the S.J. laboratory), the BLUEPRINT FP7 consortium (I.A. laboratory), the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine (I.A. laboratory), Minerva Stiftung (I.A. laboratory), The Azrieli Foundation (D.R.W.), the European Molecular Biology Organization (ALT766-2014 for D.R.W.) and the European Commission FP7 (Marie Curie Actions, EMBOCOFUND2012, GA-2012-600394 for D.R.W.).
The authors declare no competing financial interests.
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Amit, I., Winter, D. & Jung, S. The role of the local environment and epigenetics in shaping macrophage identity and their effect on tissue homeostasis. Nat Immunol 17, 18–25 (2016) doi:10.1038/ni.3325
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