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Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

Abstract

Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and function). Here we focus on the occurrence of phenotypically distinct subpopulations in three lineages of myeloid cells with important roles in innate and acquired immunity: macrophages, mast cells and neutrophils. Cytokine signals, epigenetic modifications and other microenvironmental factors can substantially and, in some cases, rapidly and reversibly alter the phenotype of these cells and influence their function. This suggests that regulation of the phenotype and function of differentiated hematopoietic cells by microenvironmental factors, including those generated during immune responses, represents a common mechanism for modulating innate or adaptive immunity.

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Figure 1: Macrophage populations and functional subsets.
Figure 2: Mast-cell populations and patterns of functional activation.
Figure 3: Features shared by 'neutrophil MDSCs' and neutrophils in mice with polymicrobial infection.

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Acknowledgements

We thank M. Tsai and J. Kalesnikoff for discussions; and J. Lilla for help with Figure 2. Supported by the US National Institutes of Health (AI70813, AI23990 and CA72074 to S.J.G.), the Danish National Research Council (N.B.) and the intramural research program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health (T.A.W.).

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Galli, S., Borregaard, N. & Wynn, T. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol 12, 1035–1044 (2011). https://doi.org/10.1038/ni.2109

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