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Molecular control of activation and priming in macrophages

Nature Immunology volume 17, pages 26–33 (2016)Cite this article

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Abstract

In tissues, macrophages are exposed to metabolic, homeostatic and immunoregulatory signals of local or systemic origin that influence their basal functions and responses to danger signals. Signal-transduction pathways regulated by extracellular signals are coupled to distinct sets of broadly expressed stimulus-regulated transcription factors whose ability to elicit gene-expression changes is influenced by the accessibility of their binding sites in the macrophage genome. In turn, accessibility of macrophage-specific transcriptional regulatory elements (enhancers and promoters) is specified by transcription factors that determine the macrophage lineage or impose their tissue-specific properties. Here we review recent findings that advance the understanding of mechanisms underlying priming and signal-dependent activation of macrophages and discuss the effect of genetic variation on these processes.

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Figure 1: The interplay between homeostatic tissue signals and danger signals in the control of macrophage function.
Figure 2: Three main groups of receptors relevant to macrophage activation classified on the basis of the main transcription factors coupled to them.
Figure 3: Interplay between LDTFs and SRTFs in the control of gene expression.
Figure 4: Effect of natural genetic variation on enhancer selection and function.

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  1. Department of Cellular and Molecular Medicine and Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California, USA

    Christopher K Glass

  2. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    Gioacchino Natoli

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Correspondence to Christopher K Glass.

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Glass, C., Natoli, G. Molecular control of activation and priming in macrophages. Nat Immunol 17, 26–33 (2016). https://doi.org/10.1038/ni.3306

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