Myelin and macrophages in the PNS: An intimate relationship in trauma and disease

Macrophages of the peripheral nervous system belong to the so-called tissue macrophages, with multiple functions during injury and disease. Their origin during ontogeny has not yet been completely resolved, but it is clear that upon injury and disease conditions, they are supplemented by hematopoietic derivatives. In the peripheral nervous system, the most abundantly investigated scenario in which resident and infiltrating macrophages are involved is the so-called "Wallerian degeneration", a complex degenerative process where macrophages exhibit mostly beneficial functions by phagocytosing myelin and axonal remnants. Of special interest is the implication of macrophages in inflammatory nerve diseases, like acute Guillain-Barré syndromes and its permanent variant, chronic inflammatory demyelinating polyneuropathy, where macrophages are supposed to be substantial (co-)mediators of the diseases. In inherited peripheral neuropathies nerve macrophages possess a clear disease-amplifying function. In the corresponding animal models, a coordinated interplay between mutant Schwann cells, macrophages, endoneurial fibroblasts and the target structure, myelin, emerged. Along this process, a newly discovered disease mechanism mediated by macrophages is the dedifferentiation of myelinating Schwann cells. As macrophages are amplifiers of the genetically-mediated, non-curable diseases, targeting the mechanisms of their activation might be a promising strategy to treat these disorders. This article is part of a Special Issue entitled SI: Myelin Evolution.