Origin and Differentiation of Nerve-Associated Macrophages

The mature peripheral nervous system is a steady network structure yet shows remarkable regenerative properties. The interaction of peripheral nerves with myeloid cells has largely been investigated in the context of damage, following trauma or infection. Recently, specific macrophages dedicated to homeostatic peripheral nerves have come into focus. These macrophages are defined by tissue and nerve type, are seeded in part prenatally, and self-maintain via proliferation. Thus, they are markedly distinct from monocyte-derived macrophages invading after local disturbance of nerve integrity. The phenotypic and transcriptional adaptation of macrophages to the discrete nervous niche may exert axon guidance and nerve regeneration and thus contribute to the stability of the peripheral nervous network. Deciphering these conserved macrophage-nerve interactions offers new translational perspectives for chronic diseases of the peripheral nervous system, such as diabetic neuropathy and pain.