Peripheral nerve resident macrophages are microglia-like cells with tissue-specific programming

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 we show that self-maintaining PNS macrophages share unique features with CNS microglia. 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 or neurodegeneration. Several microglial activation-associated and PNS macrophage-enriched genes were also expressed in spinal cord microglia at steady state. While PNS macrophages arose from both embryonic and hematopoietic precursors, 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.