TY - JOUR T1 - MHCII is required for α-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. 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, PY - 2013/6/7/entrez PY - 2013/6/7/pubmed PY - 2013/8/7/medline SP - 9592 EP - 600 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 33 IS - 23 N2 - 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. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/23739956/MHCII_is_required_for_α_synuclein_induced_activation_of_microglia_CD4_T_cell_proliferation_and_dopaminergic_neurodegeneration_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=23739956 DB - PRIME DP - Unbound Medicine ER -