Therapeutic targeting of colony stimulating factor 1 receptor

Colony Stimulating Factor 1 (CSF1) is the main homeostatic macrophage growth factor acting through a lineage-restricted receptor, CSF1R. Macrophages in different activation states contribute to development, organogenesis, homeostasis and tissue repair but are also drivers of inflammatory pathology.

This opinion reviews the literature on CSF1R-dependent macrophages and the therapeutic potential of CSF1R agonism and antagonism in acute and chronic inflammatory conditions, excluding infectious and autoimmune diseases.

CSF1R agonism has shown therapeutic potential as a regenerative medicine in a broad range of tissues. Conversely, CSF1- or CSF1R-targeted macrophage depletion approaches have also demonstrated benefits in inflammatory models and relieving immunosuppression in malignancy, but sustained macrophage depletion may compromise resolution phase macrophage functions. Anti-CSF1R agents are currently approved for 2 indications: chronic graft versus host disease and tenosynovial giant cell tumors. CSF1R+ macrophages control the circulating levels of their ligands through receptor-mediated clearance. Consequently, macrophage depletion leads to a large increase in circulating CSF1 which can restore tissue macrophage populations with a more homeostatic phenotype. Thus, paradoxically, CSF1 treatment and anti-CSF1R-mediated macrophage depletion may achieve the same therapeutic outcome.