RT Journal Article
SR Electronic
T1 MHCII Is Required for α-Synuclein-Induced Activation of Microglia, CD4 T Cell Proliferation, and Dopaminergic Neurodegeneration
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9592
OP 9600
DO 10.1523/JNEUROSCI.5610-12.2013
VO 33
IS 23
A1 Harms, Ashley S.
A1 Cao, Shuwen
A1 Rowse, Amber L.
A1 Thome, Aaron D.
A1 Li, Xinru
A1 Mangieri, Leandra R.
A1 Cron, Randy Q.
A1 Shacka, John J.
A1 Raman, Chander
A1 Standaert, David G.
YR 2013
UL http://www.jneurosci.org/content/33/23/9592.abstract
AB Accumulation of α-synuclein (α-syn) in the brain is a core feature of Parkinson disease (PD) and leads to microglial activation, production 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.