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01-12-2020 | Dementia | Research

Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models

Authors: Michiyo Iba, Changyoun Kim, Michelle Sallin, Somin Kwon, Anjali Verma, Cassia Overk, Robert A. Rissman, Ranjan Sen, Jyoti Misra Sen, Eliezer Masliah

Published in: Journal of Neuroinflammation | Issue 1/2020

Abstract

Background

α-Synuclein (α-syn) is a pre-synaptic protein which progressively accumulates in neuronal and non-neuronal cells in neurodegenerative diseases such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Recent evidence suggests that aberrant immune activation may be involved in neurodegeneration in PD/DLB. While previous studies have often focused on the microglial responses, less is known about the role of the peripheral immune system in these disorders.

Methods

To understand the involvement of the peripheral immune system in PD/DLB, we evaluated T cell populations in the brains of α-syn transgenic (tg) mice (e.g., Thy1 promoter line 61) and DLB patients.

Results

Immunohistochemical analysis showed perivascular and parenchymal infiltration by CD3+/CD4+ helper T cells, but not cytotoxic T cells (CD3+/CD8+) or B cells (CD20+), in the neocortex, hippocampus, and striatum of α-syn tg mice. CD3+ cells were found in close proximity to the processes of activated astroglia, particularly in areas of the brain with significant astrogliosis, microgliosis, and expression of pro-inflammatory cytokines. In addition, a subset of CD3+ cells co-expressed interferon γ. Flow cytometric analysis of immune cells in the brains of α-syn tg mice revealed that CD1d-tet+ T cells were also increased in the brains of α-syn tg mice suggestive of natural killer T cells. In post-mortem DLB brains, we similarly detected increased numbers of infiltrating CD3+/CD4+ T cells in close proximity with blood vessels.

Conclusion

These results suggest that infiltrating adaptive immune cells play an important role in neuroinflammation and neurodegeneration in synucleinopathies and that modulating peripheral T cells may be a viable therapeutic strategy for PD/DLB.

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Title: Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models
Authors: Michiyo Iba
Changyoun Kim
Michelle Sallin
Somin Kwon
Anjali Verma
Cassia Overk
Robert A. Rissman
Ranjan Sen
Jyoti Misra Sen
Eliezer Masliah
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Dementia
Parkinson's Disease
Dementia
Published in: Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-020-01888-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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