ArticleCNS neuroscience & therapeutics2024
Treating activated regulatory T cells with pramipexole protects human dopaminergic neurons from 6-OHDA-induced degeneration.
Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Article
- The Progress of Active Immunotherapy for Parkinson's Disease.International journal of molecular sciences · 2026Review
- Targeting lineage-specific heterogeneity and hypovascular-fibrotic barriers may enable precision immunotherapy in pituitary neuroendocrine tumors.Frontiers in immunology · 2026Review
- Genetic changes in regulatory immune cells induced by pramipexole and rotigotine: implications for the treatment of Parkinson's disease.Inflammopharmacology · 2025Article
- Neuroimmune crosstalk in Parkinson's disease: the pivotal role of microglia and infiltrating T cells.Molecular biology reports · 2025Review
- Genetic Variants in CytokinesLife (Basel, Switzerland) · 2025Article
- Treating activated regulatory T cells with pramipexole protects human dopaminergic neurons from 6-OHDA-induced degeneration.CNS neuroscience & therapeutics · 2024Article
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Abstract
backgroundParkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, which promotes a sustained inflammatory environment in the central nervous system. Regulatory T cells (Tregs) play an important role in the control of inflammation and might play a neuroprotective role. Indeed, a decrease in Treg number and function has been reported in PD. In this context, pramipexole, a dopaminergic receptor agonist used to treat PD symptoms, has been shown to increase peripheral levels of Treg cells and improve their suppressive function. The aim of this work was to determine the effect of pramipexole on immunoregulatory Treg cells and its possible neuroprotective effect on human dopaminergic neurons differentiated from human embryonic stem cells.
methodsTreg cells were sorted from white blood cells of healthy human donors. Assays were performed with CD3/CD28-activated and non-activated Treg cells treated with pramipexole at concentrations of 2 or 200 ng/mL. These regulatory cells were co-cultured with in vitro-differentiated human dopaminergic neurons in a cytotoxicity assay with 6-hydroxydopamine (6-OHDA). The role of interleukin-10 (IL-10) was investigated by co-culturing activated IL-10-producing Treg cells with neurons. To further investigate the effect of treatment on Tregs, gene expression in pramipexole-treated, CD3/CD28-activated Treg cells was determined by Fluidigm analysis.
resultsPramipexole-treated CD3/CD28-activated Treg cells showed significant protective effects on dopaminergic neurons when challenged with 6-OHDA. Pramipexole-treated activated Treg cells showed neuroprotective capacity through mechanisms involving IL-10 release and the activation of genes associated with regulation and neuroprotection.
conclusionAnti-CD3/CD28-activated Treg cells protect dopaminergic neurons against 6-OHDA-induced damage. In addition, activated, IL-10-producing, pramipexole-treated Tregs also induced a neuroprotective effect, and the supernatants of these co-cultures promoted axonal growth. Pramipexole-treated, activated Tregs altered their gene expression in a concentration-dependent manner, and enhanced TGFβ-related dopamine receptor regulation and immune-related pathways. These findings open new perspectives for the development of immunomodulatory therapies for the treatment of PD.
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