PT  - JOURNAL ARTICLE
AU  - Harms, Ashley S.
AU  - Cao, Shuwen
AU  - Rowse, Amber L.
AU  - Thome, Aaron D.
AU  - Li, Xinru
AU  - Mangieri, Leandra R.
AU  - Cron, Randy Q.
AU  - Shacka, John J.
AU  - Raman, Chander
AU  - Standaert, David G.
TI  - MHCII Is Required for α-Synuclein-Induced Activation of Microglia, CD4 T Cell Proliferation, and Dopaminergic Neurodegeneration
AID  - 10.1523/JNEUROSCI.5610-12.2013
DP  - 2013 Jun 05
TA  - The Journal of Neuroscience
PG  - 9592--9600
VI  - 33
IP  - 23
4099  - http://www.jneurosci.org/content/33/23/9592.short
4100  - http://www.jneurosci.org/content/33/23/9592.full
SO  - J. Neurosci.2013 Jun 05; 33
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.