Peripheral nerve resident macrophages share tissue-specific programming and features of activated microglia

Peter L. Wang, Aldrin K. Y. Yim, Ki-Wook Kim, Denis Avey, Rafael S. Czepielewski, Marco Colonna, Jeffrey Milbrandt () and Gwendalyn J. Randolph ()
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Peter L. Wang: Washington University School of Medicine
Aldrin K. Y. Yim: Washington University School of Medicine
Ki-Wook Kim: Washington University School of Medicine
Denis Avey: Washington University School of Medicine
Rafael S. Czepielewski: Washington University School of Medicine
Marco Colonna: Washington University School of Medicine
Jeffrey Milbrandt: Washington University School of Medicine
Gwendalyn J. Randolph: Washington University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Whereas microglia are recognized as fundamental players in central nervous system (CNS) development and function, much less is known about macrophages of the peripheral nervous system (PNS). Here, by comparing gene expression across neural and conventional tissue-resident macrophages, we identified transcripts that were shared among neural resident macrophages as well as selectively enriched in PNS macrophages. Remarkably, PNS macrophages constitutively expressed genes previously identified to be upregulated by activated microglia during aging, neurodegeneration, or loss of Sall1. Several microglial activation-associated and PNS macrophage-enriched genes were also expressed in spinal cord microglia at steady state. We further show that PNS macrophages rely on IL-34 for maintenance and arise from both embryonic and hematopoietic precursors, while their expression of activation-associated genes did not differ by ontogeny. Collectively, these data uncover shared and unique features between neural resident macrophages and emphasize the role of nerve environment for shaping PNS macrophage identity.

Date: 2020
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DOI: 10.1038/s41467-020-16355-w

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