T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils [article]

Sonia George, Trevor Tyson, Nolwen Lydianne Rey, Rachael Sheridan, Wouter Peerlaerts, Katelyn Becker, Emily Schulz, Lindsay Meyerdirk, Amanda Burmeister, Jennifer Steiner, Martha L. Escobar, Jiyan Ma (+2 others)
2020 bioRxiv   pre-print
α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinsons 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
more » ... d 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. To study the role of the adaptive immune system with respect to α-syn pathology, we injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology as well as microgliosis. Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. We also reconstituted T and B cell populations in the NSG mice with cells isolated from a wildtype mouse spleen. Interestingly, reconstituting the T cell population decreased the accumulation of α-syn pathology and resulted in persistent microgliosis when compared to non-transplanted mice; reconstitution of B cells did not alter the nigral neuropathology. Our work provides experimental evidence that T cells play a role in the pathogenesis of α-synucleinopathies.
doi:10.1101/2020.02.20.956599 fatcat:jmir2iituba25lerga243lzfbe