Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease
Abstract Inflammation is a pathological hallmark of Parkinson’s disease (PD). Chronic pro-inflammatory responses contribute to the loss of neurons in the neurodegenerative process. The present study was undertaken to define the peripheral innate and adaptive immune contributions to inflammation in p...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-05-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-021-00188-5 |
| _version_ | 1797641267018989568 |
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| author | Aaron D. Thome Farah Atassi Jinghong Wang Alireza Faridar Weihua Zhao Jason R. Thonhoff David R. Beers Eugene C. Lai Stanley H. Appel |
| author_facet | Aaron D. Thome Farah Atassi Jinghong Wang Alireza Faridar Weihua Zhao Jason R. Thonhoff David R. Beers Eugene C. Lai Stanley H. Appel |
| author_sort | Aaron D. Thome |
| collection | DOAJ |
| description | Abstract Inflammation is a pathological hallmark of Parkinson’s disease (PD). Chronic pro-inflammatory responses contribute to the loss of neurons in the neurodegenerative process. The present study was undertaken to define the peripheral innate and adaptive immune contributions to inflammation in patients with PD. Immunophenotyping revealed a shift of peripheral myeloid and lymphoid cells towards a pro-inflammatory phenotype. Regulatory T cells (Tregs) were reduced in number, and their suppression of T responder proliferation decreased. The PD Tregs did not suppress activated pro-inflammatory myeloid cells. Ex vivo expansion of Tregs from patients with PD restored and enhanced their suppressive functions while expanded Tregs displayed increased expression of foxp3, il2ra (CD25), nt5e (CD73), il10, il13, ctla4, pdcd1 (PD1), and gzmb. Collectively, these findings documented a shift towards a pro-inflammatory peripheral immune response in patients with PD; the loss of Treg suppressive functions may contribute significantly to this response, supporting PD as a disorder with extensive systemic pro-inflammatory responses. The restoration and enhancement of Treg suppressive functions following ex vivo expansion may provide a potential cell therapeutic approach for patients with PD. |
| first_indexed | 2024-03-11T13:43:06Z |
| format | Article |
| id | doaj.art-31fbf101a5d54be486190d6c220e76d4 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-11T13:43:06Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-31fbf101a5d54be486190d6c220e76d42023-11-02T11:09:16ZengNature Portfolionpj Parkinson's Disease2373-80572021-05-017111210.1038/s41531-021-00188-5Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s diseaseAaron D. Thome0Farah Atassi1Jinghong Wang2Alireza Faridar3Weihua Zhao4Jason R. Thonhoff5David R. Beers6Eugene C. Lai7Stanley H. Appel8Department of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalDepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalDepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalDepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalDepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalDepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalDepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalDepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalDepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist HospitalAbstract Inflammation is a pathological hallmark of Parkinson’s disease (PD). Chronic pro-inflammatory responses contribute to the loss of neurons in the neurodegenerative process. The present study was undertaken to define the peripheral innate and adaptive immune contributions to inflammation in patients with PD. Immunophenotyping revealed a shift of peripheral myeloid and lymphoid cells towards a pro-inflammatory phenotype. Regulatory T cells (Tregs) were reduced in number, and their suppression of T responder proliferation decreased. The PD Tregs did not suppress activated pro-inflammatory myeloid cells. Ex vivo expansion of Tregs from patients with PD restored and enhanced their suppressive functions while expanded Tregs displayed increased expression of foxp3, il2ra (CD25), nt5e (CD73), il10, il13, ctla4, pdcd1 (PD1), and gzmb. Collectively, these findings documented a shift towards a pro-inflammatory peripheral immune response in patients with PD; the loss of Treg suppressive functions may contribute significantly to this response, supporting PD as a disorder with extensive systemic pro-inflammatory responses. The restoration and enhancement of Treg suppressive functions following ex vivo expansion may provide a potential cell therapeutic approach for patients with PD.https://doi.org/10.1038/s41531-021-00188-5 |
| spellingShingle | Aaron D. Thome Farah Atassi Jinghong Wang Alireza Faridar Weihua Zhao Jason R. Thonhoff David R. Beers Eugene C. Lai Stanley H. Appel Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease npj Parkinson's Disease |
| title | Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease |
| title_full | Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease |
| title_fullStr | Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease |
| title_full_unstemmed | Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease |
| title_short | Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease |
| title_sort | ex vivo expansion of dysfunctional regulatory t lymphocytes restores suppressive function in parkinson s disease |
| url | https://doi.org/10.1038/s41531-021-00188-5 |
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