Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 265, Issue 1-2, Pages 1-10Publisher
ELSEVIER
DOI: 10.1016/j.jneuroim.2013.10.009
Keywords
Parkinson's disease; Neuroprotection; Regulatory T cells; Innate immunity; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Neuroinflammation
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Funding
- Carol Swans Neuroscience Research Laboratory
- Frances and Louie Blumkin Foundation
- National Institutes of Health [P01 DA028555, R01 NS36126, P01 NS31492, 2R01 NS034239, P01 MH64570, P01 NS43985, R01 NS070190]
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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 MITI? 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. (C) 2013 Elsevier B.V. All rights reserved.
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