Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models
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 im...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-01888-0 |
| _version_ | 1819107671571169280 |
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| author | Michiyo Iba Changyoun Kim Michelle Sallin Somin Kwon Anjali Verma Cassia Overk Robert A. Rissman Ranjan Sen Jyoti Misra Sen Eliezer Masliah |
| author_facet | Michiyo Iba Changyoun Kim Michelle Sallin Somin Kwon Anjali Verma Cassia Overk Robert A. Rissman Ranjan Sen Jyoti Misra Sen Eliezer Masliah |
| author_sort | Michiyo Iba |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T02:57:45Z |
| format | Article |
| id | doaj.art-657c01bd46334aa8b858a0ce687a1508 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-22T02:57:45Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-657c01bd46334aa8b858a0ce687a15082022-12-21T18:41:14ZengBMCJournal of Neuroinflammation1742-20942020-07-0117111410.1186/s12974-020-01888-0Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic modelsMichiyo Iba0Changyoun Kim1Michelle Sallin2Somin Kwon3Anjali Verma4Cassia Overk5Robert A. Rissman6Ranjan Sen7Jyoti Misra Sen8Eliezer Masliah9Laboratory of Neurogenetics, Molecular Neuropathology Section, National Institute on Aging, National Institutes of HealthLaboratory of Neurogenetics, Molecular Neuropathology Section, National Institute on Aging, National Institutes of HealthLaboratory of Clinical Investigation, Immune Cells and Inflammation Section, National Institute on Aging, National Institutes of HealthLaboratory of Neurogenetics, Molecular Neuropathology Section, National Institute on Aging, National Institutes of HealthLaboratory of Clinical Investigation, Immune Cells and Inflammation Section, National Institute on Aging, National Institutes of HealthDepartment of Neurosciences, University of California, San DiegoDepartment of Neurosciences, University of California, San DiegoLaboratory of Molecular Biology and Immunology, Gene Regulation Section, Biomedical Research Center, National Institute on Aging, National Institutes of HealthLaboratory of Clinical Investigation, Immune Cells and Inflammation Section, National Institute on Aging, National Institutes of HealthLaboratory of Neurogenetics, Molecular Neuropathology Section, National Institute on Aging, National Institutes of HealthAbstract 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.http://link.springer.com/article/10.1186/s12974-020-01888-0α-SynucleinT cellParkinson’s diseaseDementia with Lewy BodiesAdaptive immunityInnate immunity |
| spellingShingle | Michiyo Iba Changyoun Kim Michelle Sallin Somin Kwon Anjali Verma Cassia Overk Robert A. Rissman Ranjan Sen Jyoti Misra Sen Eliezer Masliah Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models Journal of Neuroinflammation α-Synuclein T cell Parkinson’s disease Dementia with Lewy Bodies Adaptive immunity Innate immunity |
| title | Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models |
| title_full | Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models |
| title_fullStr | Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models |
| title_full_unstemmed | Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models |
| title_short | Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models |
| title_sort | neuroinflammation is associated with infiltration of t cells in lewy body disease and α synuclein transgenic models |
| topic | α-Synuclein T cell Parkinson’s disease Dementia with Lewy Bodies Adaptive immunity Innate immunity |
| url | http://link.springer.com/article/10.1186/s12974-020-01888-0 |
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