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

Nature
Dmitri LodyginAlexander Flügel

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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Methods Mentioned

BETA
transgenic
nuclear translocation
enzyme-linked immunosorbent assay
PCR
biopsies
flow cytometry
flow
fluorescence-activated cell sorting
FACS
RNA-seq

Software Mentioned

Ismatec
Creative BioMart
GraphPad
GraphPad Prism
Imaris
Zeiss ZEN
Fiji
Cell Quest
ImageJ
BZ

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