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MHCII is required for α-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration.
J Neurosci. 2013 Jun 05; 33(23):9592-600.JN

Abstract

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.

Authors+Show Affiliations

Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23739956

Citation

Harms, Ashley S., et al. "MHCII Is Required for Α-synuclein-induced Activation of Microglia, CD4 T Cell Proliferation, and Dopaminergic Neurodegeneration." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 33, no. 23, 2013, pp. 9592-600.
Harms AS, Cao S, Rowse AL, et al. MHCII is required for α-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. J Neurosci. 2013;33(23):9592-600.
Harms, A. S., Cao, S., Rowse, A. L., Thome, A. D., Li, X., Mangieri, L. R., Cron, R. Q., Shacka, J. J., Raman, C., & Standaert, D. G. (2013). MHCII is required for α-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 33(23), 9592-600. https://doi.org/10.1523/JNEUROSCI.5610-12.2013
Harms AS, et al. MHCII Is Required for Α-synuclein-induced Activation of Microglia, CD4 T Cell Proliferation, and Dopaminergic Neurodegeneration. J Neurosci. 2013 Jun 5;33(23):9592-600. PubMed PMID: 23739956.
* Article titles in AMA citation format should be in sentence-case
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 -