GM-CSF induces neuroprotective and anti-inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxicated mice

Abstract

Innate and adaptive immune responses can speed nigrostriatal neurodegeneration in Parkinson's disease (PD). We posit that GM-CSF can attenuate such responses. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, GM-CSF given prior to MPTP protected nigral dopaminergic neurons coincident with altered microglial morphologies and regulatory T cell (Treg) induction. Adoptive transfer of GM-CSF-induced Treg to MPTP mice protected nigral neurons. Gene expression analyses revealed novel immune-based neuronal protection pathways linked to the upregulation of IL-27. The results provide evidence that GM-CSF modulation of immunity could be of clinical benefit for PD.

Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Innate immunity; Neuroinflammation; Neuroprotection; Parkinson's disease; Regulatory T cells.