Cell-Surface and Secreted Isoforms of CSF-1 Exert Opposing Roles in Macrophage-Mediated Neural Damage in Cx32-Deficient Mice.

Mouse models of Charcot-Marie-Tooth neuropathy have indicated that low-grade secondary inflammation involving phagocytosing macrophages amplifies demyelination, Schwann cell dedifferentiation, and perturbation of axons. The recruitment and pathogenic activation of detrimental macrophages is regulated by CSF-1, a cytokine that is mostly expressed by fibroblasts in the diseased nerve and exists in three isoforms. We show that the cell-surface and secreted isoforms of CSF-1 have opposing effects on macrophage activation and disease progression in a mouse model of CMT1X. These insights into opposing functions of disease-modulating cytokine isoforms might enable the development of specific therapeutic approaches.