title: α-Synuclein deficiency promotes neuroinflammation by increasing Th1 cell-mediated immune responses.
abstract: Increased α-synuclein immunoreactivity has been associated with inflammatory activity in multiple sclerosis (MS) lesions, but the function of α-synuclein in neuroinflammation remains unknown. The aim of this study was to examine the role of α-synuclein in immunological processes in murine experimental autoimmune encephalomyelitis (EAE) as a model of MS.
  
  
  
  We studied EAE in wildtype (aSyn(+/+)) and α-synuclein knockout (aSyn(-/-)) mice on a C57BL/6N background. In the spleen and spinal cord of aSyn(+/+) mice, we observed a gradual reduction of α-synuclein expression during EAE, starting already in the pre-symptomatic disease phase. Compared to aSyn(+/+) mice, aSyn(-/-) mice showed an earlier onset of symptoms but no differences in symptom severity at the peak of disease. Earlier symptom onset was accompanied by increased spinal cord infiltration of CD4(+) T cells, predominantly of interferon-γ-producing T helper 1 (Th1) cells, and reduced infiltration of regulatory T cells, whereas antigen-presenting cells were unaltered. Pre-symptomatically, aSyn(-/-) mice exhibited hyperproliferative CD4(+) splenocytes consistent with increased splenic interleukin-2 mRNA expression, resulting in increased numbers of Th1 cells in the spleen at the onset of symptoms.
  
  
  
  Our findings indicate a functional role of α-synuclein in early EAE by increasing Th1 cell-mediated immune response.
authors: Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany.
authors: Benjamin
authors: B
authors: Ettle
authors: Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany.
authors: Kristina
authors: K
authors: Kuhbandner
authors: Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany.
authors: Stefanie
authors: S
authors: Jörg
authors: Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany.
authors: Alana
authors: A
authors: Hoffmann
authors: Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany.
authors: Jürgen
authors: J
authors: Winkler
authors: Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany. ralf.linker@uk-erlangen.de.
authors: Ralf A
authors: RA
authors: Linker
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D012333:RNA, Messenger; D013116:Spinal Cord / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology*; D051844:alpha-Synuclein / Q000172:deficiency* / Q000235:genetics
chemical_list: D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; D051844:alpha-Synuclein; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: Experimental autoimmune encephalomyelitis; Multiple sclerosis; Neuroinflammation; α-Synuclein