alpha-synuclein and myelin-oligodendrocyte-glycoprotein-(35-55)

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.

Topics: alpha-Synuclein; Analysis of Variance; Animals; Antigen-Presenting Cells; Cell Proliferation; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Gene Expression Regulation; Mice; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; RNA, Messenger; Spinal Cord; Th1 Cells