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

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...

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Bibliographic Details
Published in:	Journal of neuroinflammation 2020-07, Vol.17 (1), p.214-214, Article 214
Main Authors:	Iba, Michiyo, Kim, Changyoun, Sallin, Michelle, Kwon, Somin, Verma, Anjali, Overk, Cassia, Rissman, Robert A, Sen, Ranjan, Sen, Jyoti Misra, Masliah, Eliezer
Format:	Article
Language:	eng
Subjects:	Adaptive immunity Adaptive Immunity - physiology Age Aged Aged, 80 and over alpha-Synuclein - immunology alpha-Synuclein - metabolism Animals Antigen presentation Astrocytes Atrophy Autopsy Blood vessels Brain - immunology Brain - metabolism Brain - pathology Brain research CD1d antigen CD20 antigen CD3 antigen CD4 antigen CD8 antigen Cytokines Cytotoxicity Dementia Dementia disorders Dementia with Lewy Bodies Female Flow cytometry Gene expression Gliosis Humans Immune system Inflammation Inflammation - immunology Inflammation - metabolism Inflammation - pathology Innate immunity Lewy Body Disease - immunology Lewy Body Disease - metabolism Lewy Body Disease - pathology Lymphocytes Lymphocytes B Lymphocytes T Male Mice Mice, Transgenic Movement disorders Neocortex Neostriatum Neurodegeneration Neurodegenerative diseases Neurons Parkinson's disease T cell T-Lymphocytes - immunology T-Lymphocytes - metabolism T-Lymphocytes - pathology Transgenic mice α-Synuclein γ-Interferon
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Summary:	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. 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. 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. 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.
ISSN:	1742-2094 1742-2094