Open AccessT Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils
Author(s) -
Sonia George,
Trevor Tyson,
Nolwen L. Rey,
Rachael Sheridan,
Wouter Peelaerts,
Katelyn Becker,
Emily Schulz,
Lindsay Meyerdirk,
Amanda R. Burmeister,
Christian Ulrich von Linstow,
Jennifer A. Steiner,
Martha L. Escobar Galvis,
Jiyan Ma,
J. Andrew Pospisilik,
Viviane Labrie,
Lena Brundin,
Patrik Brundin
Publication year - 2021
Publication title -
journal of parkinson's disease/journal of parkinson's disease (online)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.747
H-Index - 45
eISSN - 1877-718X
pISSN - 1877-7171
DOI - 10.3233/jpd-202351
Subject(s) - substantia nigra , microglia , adoptive cell transfer , alpha synuclein , pathology , neuroinflammation , pathogenesis , biology , immune system , population , t cell , synucleinopathies , immunology , parkinson's disease , inflammation , medicine , disease , environmental health
Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α-synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.