| First Author | Harms AS | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 23 | Pages | 9592-600 |
| PubMed ID | 23739956 | Mgi Jnum | J:198648 |
| Mgi Id | MGI:5498600 | Doi | 10.1523/JNEUROSCI.5610-12.2013 |
| Citation | Harms AS, et al. (2013) MHCII is required for alpha-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. J Neurosci 33(23):9592-600 |
| abstractText | Accumulation of alpha-synuclein (alpha-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 alpha-syn as well as in vitro systems to study the role of the MHCII complex in alpha-syn-induced neuroinflammation and neurodegeneration. We find that in vivo, expression of full-length human alpha-syn causes striking induction of MHCII expression by microglia, while knock-out of MHCII prevents alpha-syn-induced microglial activation, antigen presentation, IgG deposition, and the degeneration of dopaminergic neurons. In vitro, treatment of microglia with aggregated alpha-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 alpha-syn in PD and suggest that the MHCII signaling complex may be a target of neuroprotective therapies for the disease. |
