CSF-1 maintains pathogenic but not homeostatic myeloid cells in the central nervous system during autoimmune neuroinflammation.

Abstract The receptor for colony stimulating factor 1 (CSF-1R) is important the survival and function of myeloid cells that mediate pathology during experimental autoimmune encephalomyelitis (EAE), an animal model multiple sclerosis (MS). CSF-1 IL-34, ligands CSF-1R, have similar bio-activities but distinct tissue context-dependent expression patterns, suggesting they different roles. This could be case in EAE, given upregulated CNS, while IL-34 remains constitutively expressed. We found targeting with neutralizing antibody halted ongoing efficacy superior to CSF-1R inhibitor BLZ945, whereas neutralization had no effect, pathogenic were maintained by CSF-1. Both anti-CSF-1 BLZ945 treatment greatly reduced number monocyte-derived microglia CNS. However, selectively depleted inflammatory monocytes inflamed CNS areas, virtually all cells, including quiescent microglia, throughout Anti-CSF-1 size demyelinated lesions microglial activation grey matter. Lastly, we bone marrow-derived immune major mediators CSF-1R-dependent pathology, played a lesser role. Our findings suggest effective ameliorating MS preserving homeostatic functions thereby minimizing risks associated ablation cells. National Multiple Sclerosis Society (RG-1803-30491) Institutes Health T32 training grant (T32AI134646, NIAID)