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  β-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration.

Lodygin, D., Hermann, M., Schweingruber, N., Flügel-Koch, C., Watanabe, T., Schlosser, C., et al. (2019). β-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration. Nature, 566, 503-508. doi:10.1038/s41586-019-0964-2.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-0FAB-D Version Permalink: http://hdl.handle.net/21.11116/0000-0003-B57F-3
Genre: Journal Article

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 Creators:
Lodygin, D., Author
Hermann, M., Author
Schweingruber, N., Author
Flügel-Koch, C., Author
Watanabe, T.1, Author              
Schlosser, C., Author
Merlini, A., Author
Körner, H., Author
Chang, H. F., Author
Fischer, H. J., Author
Reichardt, H. M., Author
Zagrebelsky, M., Author
Mollenhauer, B., Author
Kügler, S., Author
Fitzner, D., Author
Frahm, J.1, Author              
Stadelmann, C., Author
Haberl, M., Author
Odoardi, F., Author
Flügel, A., Author
Affiliations:
1Biomedical NMR Research GmbH, MPI for biophysical chemistry, Max Planck Society, ou_578634              

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 Abstract: The grey matter is a central target of pathological processes in neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. The grey matter is often also affected in multiple sclerosis, an autoimmune disease of the central nervous system. The mechanisms that underlie grey matter inflammation and degeneration in multiple sclerosis are not well understood. Here we show that, in Lewis rats, T cells directed against the neuronal protein β-synuclein specifically invade the grey matter and that this is accompanied by the presentation of multifaceted clinical disease. The expression pattern of β-synuclein induces the local activation of these T cells and, therefore, determined inflammatory priming of the tissue and targeted recruitment of immune cells. The resulting inflammation led to significant changes in the grey matter, which ranged from gliosis and neuronal destruction to brain atrophy. In humans, β-synuclein-specific T cells were enriched in patients with chronic-progressive multiple sclerosis. These findings reveal a previously unrecognized role of β-synuclein in provoking T-cell-mediated pathology of the central nervous system.

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Language(s): eng - English
 Dates: 2019-02-202019
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/s41586-019-0964-2
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Title: Nature
Source Genre: Journal
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Pages: - Volume / Issue: 566 Sequence Number: - Start / End Page: 503 - 508 Identifier: -