α-Synuclein deficiency promotes neuroinflammation by increasing Th1 cell-mediated immune responses
Open Access
- 26 August 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Neuroinflammation
- Vol. 13 (1), 1-7
- https://doi.org/10.1186/s12974-016-0694-4
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.Keywords
Funding Information
- Interdisciplinary Center for Clinical Research Erlangen (E24, E24)
- German Parkinson Association
- Deutsche Forschungsgemeinschaft (RTG 2162)
This publication has 19 references indexed in Scilit:
- Infiltrating T lymphocytes reduce myeloid phagocytosis activity in synucleinopathy modelJournal of Neuroinflammation, 2016
- Neuroinflammation in SynucleinopathiesBrain Pathology, 2016
- Alpha-Synuclein Expression in the Oligodendrocyte Lineage: an In Vitro and In Vivo Study Using Rodent and Human ModelsStem Cell Reports, 2015
- Inflammatory dysregulation of blood monocytes in Parkinson’s disease patientsActa Neuropathologica, 2014
- Association of α-Synuclein Immunoreactivity With Inflammatory Activity in Multiple Sclerosis LesionsJournal of Neuropathology and Experimental Neurology, 2009
- Red Blood Cells Are the Major Source of Alpha-Synuclein in BloodNeurodegenerative Diseases, 2008
- Demonstration of α-Synuclein Immunoreactivity in Neuronal and Glial Cytoplasm in Normal Human Brain Tissue Using Proteinase K and Formic Acid PretreatmentExperimental Neurology, 2002
- Expression Patterns of α-Synuclein in Human Hematopoietic Cells and in Drosophila at Different Developmental StagesMolecules and Cells, 2000
- Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine SystemNeuron, 2000
- Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodiesNeuroscience Letters, 1998