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...

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Autores principales:	Aaron D. Thome, Farah Atassi, Jinghong Wang, Alireza Faridar, Weihua Zhao, Jason R. Thonhoff, David R. Beers, Eugene C. Lai, Stanley H. Appel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/31fbf101a5d54be486190d6c220e76d4
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spelling	oai:doaj.org-article:31fbf101a5d54be486190d6c220e76d42021-12-02T15:54:55ZEx vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease10.1038/s41531-021-00188-52373-8057https://doaj.org/article/31fbf101a5d54be486190d6c220e76d42021-05-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00188-5https://doaj.org/toc/2373-8057Abstract 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.Aaron D. ThomeFarah AtassiJinghong WangAlireza FaridarWeihua ZhaoJason R. ThonhoffDavid R. BeersEugene C. LaiStanley H. AppelNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 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
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.
format	article
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
title	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_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_sort	ex vivo expansion of dysfunctional regulatory t lymphocytes restores suppressive function in parkinson’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/31fbf101a5d54be486190d6c220e76d4
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Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease

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