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Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice

OBJECTIVE: Parkinson’s disease (PD) is a degenerative disorder characterized by steady motor function loss. PD pathogenesis remains inconclusive, but aberrant immune responses might play important roles. We hypothesized that imbalance between T helper (Th) 1 and regulatory T (Treg) cells was essenti...

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Autores principales: Li, Wenjie, Luo, Yuan, Xu, Hongyu, Ma, Qianqian, Yao, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053775/
https://www.ncbi.nlm.nih.gov/pubmed/33853440
http://dx.doi.org/10.1177/0300060521998471
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author Li, Wenjie
Luo, Yuan
Xu, Hongyu
Ma, Qianqian
Yao, Qi
author_facet Li, Wenjie
Luo, Yuan
Xu, Hongyu
Ma, Qianqian
Yao, Qi
author_sort Li, Wenjie
collection PubMed
description OBJECTIVE: Parkinson’s disease (PD) is a degenerative disorder characterized by steady motor function loss. PD pathogenesis remains inconclusive, but aberrant immune responses might play important roles. We hypothesized that imbalance between T helper (Th) 1 and regulatory T (Treg) cells was essential in experimental PD. METHODS: Th1 and Treg cells from the blood of patients with PD and healthy volunteer blood were measured by flow cytometry. Experimental PD was induced in mice by peritoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Experimental PD severity was measured by open field test behavior assessments (distance moved, rearing, and grooming). Mice were administered neutralizing anti-tumor necrosis factor (TNF) α to inhibit Th1 effects. Treg cells were depleted by anti-CD25 neutralizing antibodies or isolated and transferred to experimental PD mice. RESULTS: Patients with PD had fewer Treg and more Th1 cells than healthy volunteers. Experimental PD mice exhibited fewer Treg and more Th1 cells. Treg cell depletion exacerbated experimental PD, whereas TNFα neutralization attenuated PD in mice. Treg transfer to experimental PD mice reduced PD severity. Mechanistically, anti-TNFα antibody administration and Treg transfer increased Treg and reduced Th1 cell abundance in the brain. CONCLUSION: Th1 and Treg cell imbalance plays an essential role in mouse experimental PD pathogenesis.
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spelling pubmed-80537752021-05-03 Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice Li, Wenjie Luo, Yuan Xu, Hongyu Ma, Qianqian Yao, Qi J Int Med Res Pre-Clinical Research Report OBJECTIVE: Parkinson’s disease (PD) is a degenerative disorder characterized by steady motor function loss. PD pathogenesis remains inconclusive, but aberrant immune responses might play important roles. We hypothesized that imbalance between T helper (Th) 1 and regulatory T (Treg) cells was essential in experimental PD. METHODS: Th1 and Treg cells from the blood of patients with PD and healthy volunteer blood were measured by flow cytometry. Experimental PD was induced in mice by peritoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Experimental PD severity was measured by open field test behavior assessments (distance moved, rearing, and grooming). Mice were administered neutralizing anti-tumor necrosis factor (TNF) α to inhibit Th1 effects. Treg cells were depleted by anti-CD25 neutralizing antibodies or isolated and transferred to experimental PD mice. RESULTS: Patients with PD had fewer Treg and more Th1 cells than healthy volunteers. Experimental PD mice exhibited fewer Treg and more Th1 cells. Treg cell depletion exacerbated experimental PD, whereas TNFα neutralization attenuated PD in mice. Treg transfer to experimental PD mice reduced PD severity. Mechanistically, anti-TNFα antibody administration and Treg transfer increased Treg and reduced Th1 cell abundance in the brain. CONCLUSION: Th1 and Treg cell imbalance plays an essential role in mouse experimental PD pathogenesis. SAGE Publications 2021-04-14 /pmc/articles/PMC8053775/ /pubmed/33853440 http://dx.doi.org/10.1177/0300060521998471 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Pre-Clinical Research Report
Li, Wenjie
Luo, Yuan
Xu, Hongyu
Ma, Qianqian
Yao, Qi
Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice
title Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice
title_full Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice
title_fullStr Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice
title_full_unstemmed Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice
title_short Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice
title_sort imbalance between t helper 1 and regulatory t cells plays a detrimental role in experimental parkinson’s disease in mice
topic Pre-Clinical Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053775/
https://www.ncbi.nlm.nih.gov/pubmed/33853440
http://dx.doi.org/10.1177/0300060521998471
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