Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models
Autor: | Eliezer Masliah, Anjali Verma, Robert A. Rissman, Cassia R. Overk, Michelle A. Sallin, Changyoun Kim, Jyoti Misra Sen, Somin Kwon, Michiyo Iba, Ranjan Sen |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Lewy Body Disease
Male Pathology medicine.medical_specialty T cell T-Lymphocytes Immunology Adaptive immunity Mice Transgenic Biology lcsh:RC346-429 Cellular and Molecular Neuroscience Mice Immune system medicine Cytotoxic T cell Animals Humans Dementia with Lewy Bodies Neuroinflammation lcsh:Neurology. Diseases of the nervous system Aged Synucleinopathies Aged 80 and over Inflammation α-Synuclein Innate immunity Innate immune system General Neuroscience Research Brain Natural killer T cell Acquired immune system nervous system diseases medicine.anatomical_structure Neurology nervous system alpha-Synuclein Parkinson’s disease Female |
Zdroj: | Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-14 (2020) Journal of Neuroinflammation |
ISSN: | 1742-2094 |
DOI: | 10.1186/s12974-020-01888-0 |
Popis: | 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. |
Databáze: | OpenAIRE |
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