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

Dmitri Lodygin, Moritz Hermann, Nils Schweingruber, Cassandra Flügel-Koch, Takashi Watanabe, Corinna Schlosser, Arianna Merlini, Henrike Körner, Hsin-Fang Chang, Henrike J. Fischer, Holger M. Reichardt, Marta Zagrebelsky, Brit Mollenhauer, Sebastian Kügler, Dirk Fitzner, Jens Frahm, Christine Stadelmann, Michael Haberl, Francesca Odoardi () and Alexander Flügel ()
Additional contact information
Dmitri Lodygin: University Medical Center Göttingen
Moritz Hermann: University Medical Center Göttingen
Nils Schweingruber: University Medical Center Göttingen
Cassandra Flügel-Koch: Friedrich-Alexander-University Erlangen-Nürnberg
Takashi Watanabe: Biomedizinische NMR, Max-Planck-Institut für biophysikalische Chemie
Corinna Schlosser: University Medical Center Göttingen
Arianna Merlini: University Medical Center Göttingen
Henrike Körner: University Medical Center Göttingen
Hsin-Fang Chang: University Medical Center Göttingen
Henrike J. Fischer: University Medical Center Göttingen
Holger M. Reichardt: University Medical Center Göttingen
Marta Zagrebelsky: Technical University Braunschweig
Brit Mollenhauer: Paracelsus-Elena-Klinik Kassel
Sebastian Kügler: University Medical Center Göttingen
Dirk Fitzner: University Medical Center Göttingen
Jens Frahm: Biomedizinische NMR, Max-Planck-Institut für biophysikalische Chemie
Christine Stadelmann: University Medical Center Göttingen
Michael Haberl: University Medical Center Göttingen
Francesca Odoardi: University Medical Center Göttingen
Alexander Flügel: University Medical Center Göttingen

Nature, 2019, vol. 566, issue 7745, 503-508

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-0964-2

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