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- Title
MHCII Is Required for α-Synuclein-Induced Activation of Microglia, CD4 T Cell Proliferation, and Dopaminergic Neurodegeneration.
- Authors
Harms, Ashley S.; Shuwen Cao; Rowse, Amber L.; Thome, Aaron D.; Xinru Li; Mangieri, Leandra R.; Cron, Randy Q.; Shacka, John J.; Raman, Chander; Standaert, David G.
- Abstract
Accumulation of α-synuclein (a-syn) in the brain is a core feature of Parkinson disease (PD) and leads to microglial activation, produc-tion of inflammatory cytokines and chemokines, T-cell infiltration, and neurodegeneration. Here, we have used both an in vivo mouse model induced by viral overexpression of α-syn as well as in vitro systems to study the role of the MHCII complex in α-syn-induced neuroinflammation and neurodegeneration. We find that in vivo, expression of full-length human α-syn causes striking induction of MHCII expression by microglia, while knock-out of MHCII prevents α-syn-induced microglial activation, antigen presentation, IgG deposition, and the degeneration of dopaminergic neurons. In vitro, treatment of microglia with aggregated α-syn leads to activation of antigen processing and presentation of antigen sufficient to drive CD4 T-cell proliferation and to trigger cytokine release. These results indicate a central role for microglial MHCII in the activation of both the innate and adaptive immune responses to α-syn in PD and suggest that the MHCII signaling complex may be a target of neuroprotective therapies for the disease.
- Subjects
MAJOR histocompatibility complex; ALPHA-synuclein; MICROGLIA; T cells; CELL proliferation; DOPAMINERGIC neurons; NEURODEGENERATION
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 23, p9592
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5610-12.2013