MHCII is required for α-Synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration

Academic Article


  • 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. © 2013 the authors.
  • Digital Object Identifier (doi)

    Pubmed Id

  • 2555363
  • Author List

  • Harm AS; Cao S; Rowse AL; Thome AD; Li X; Mangieri LR; Cron RQ; Shacka JJ; Raman C; Standaert DG
  • Start Page

  • 9592
  • End Page

  • 9600
  • Volume

  • 33
  • Issue

  • 23