Huang, Y., Liu, Z., Cao, B. et al. Treg Cells Attenuate Neuroinflammation and Protect Neurons in a Mouse Model of Parkinson’s Disease. J Neuroimmune Pharmacol 15, 224–237 (2020).
Regulatory T cells (Tregs), which secrete transforming growth factor (TGF)-β and interleukin (IL)-10, have essential role in antiinflammatory and neurotrophic functions. Herein, we explore the neuroprotection of Tregs in Parkinson’s disease (PD) by
adoptive transfer of Tregs. Tregs, isolated by magnetic sorting, were activated in vitro and then were adoptively transferred to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mice. Neuroinflammation, dopaminergic neuronal loss and behavioral changes of PD mice were evaluated. Live cell imaging system detected a dynamic contact of Tregs with MN9D cells that were stained with CD45 and galectin-1, respectively. Tregs prevented MPTP-induced dopaminergic neuronal loss, behavioral changes, and attenuated the inflammatory reaction in the brain. When blockade the LFA-1 activity in Tregs or the ICAM-1 activity in endothelial cells, the percentage of Tregs in substantia nigra (SN) decreased. CD45 and galectin-1 were expressed by Tregs and MN9D cells, respectively. CD45-labeled Tregs dynamically contacted with galectin-1-labeled MN9D cells. Inhibiting CD45 in Tregs impaired the ability of Tregs to protect dopaminergic neurons against MPP+ toxicity. Similarly, galectin-1 knockdown in MN9D cells reduced the ability of Tregs neuroprotection. Adoptive transfer of Tregs protects dopaminergic neurons in PD mice by a cell-to-cell contact mechanism underlying CD45-galectin-1 interaction.
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ElliotGreen
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Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuronal loss in the nigrostriatal system. Up to now, only symptomatic therapies are available (Savitt et al. 2006). Neuroinflammation has been largely reported to be involved in PD pathogenesis. The major factor of such neuroinflammatory responses is the activated microglia, which found in and around the degenerating dopaminergic neurons (Czlonkowska et al. 1996; Long-Smith et al. 2010; Barcia et al. 2011; Cao et al. 2011).
The microglial activation impacts on dopaminergic neuronal deterioration through the release of proinflammatory mediators, such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, and consequently damaged neurons release aggregated proteins such as nitrated αsynunclein. Activated microglia may respond to these proteins by secreting more proinflammatory factors that perpetuate neuronal injury and death (Qin et al. 2007). Furthermore, nitrated α-synunclein may drain to the periphery and induce effector T cell responses which contribute to microglia activation and accelerate neurodegeneration. The antigenic and molecular bases for these T cell-mediated neurodegenerative activities are unclear. However, recent works demonstrated that nitrated α-synunclein are recognized by the adaptive immune arm to yield antigen-specific effector T cells, which exacerbate neuroinflammation and accelerate nigrostriatal degeneration (Benner et al. 2008). In contrast, regulatory T cells (Tregs) inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration and neuroinflammation (Reynolds et al. 2007; Banerjee et al. 2008; Gee et al. 2008; Liu et al. 2009; Reynolds et al. 2009a). Actually, Tregs, the Foxp3-expressing CD4+ CD25+ T lymphocytes, which secrete transforming growth factor (TGF)-β and IL-10, are termed “suppressor cells”. Evidence shows that Tregs are not only important for maintaining immune balance at the periphery but also contribute to self-tolerance and immune privilege in the central nervous system (Singer et al. 2014; Danikowski et al. 2017). This is in keeping with their essential role in antiinflammatory and neurotrophic functions (Cederbom et al. 2000; Thornton and Shevach. 2000; Reynolds et al. 2007; Tiemessen et al. 2007; Liu et al. 2009).
Based on these observations, we hypothesized that CD4+ CD25+ Tregs modulate immune response in the brain, perhaps through interactions with the dopaminergic neurons in the nervous system, resulting in significant neuroprotection in PD models. To investigate this possibility, Tregs were isolated by magnetic sorting and activated in vitro with anti-CD3 and anti-CD-28 antibodies. Activated Tregs were adoptively transferred to MPTP-intoxicated mice, and neuroinflammation and neuronal survival were evaluated. As few as 5 × 106 Tregs were sufficient to reduce the neuroinflammation and protect dopaminergic neurons in the substantia nigra pars compacta (SNpc). These results support the use of therapeutic strategies, which induce Tregs responses to inhibit neuroinflammation and attenuate dopaminergic neurodegeneration associated with PD.
T cells can cross the blood brain barrier under certain circumstances, so there is the possibility that a treatment of this nature could be administered via IV.
"mouse model", not just any mice but lab mice raised for the job.
"Induced PD like symptoms"
Since mice do not get PD, not even a mousy version, they are given a decease that looks like PD.
Any time a researcher needs some attention or a research grant they do one of these mouse things . Sorry to rain on your parade but there are so many like this sucking up research money.
I agree with you up to a point. Mice are not humans, and a chemically induced model of PD may be very different from real PD in important ways.
However, sometimes if you read a few key words and dismiss an article out of hand--it can mean you miss out! I think that's the case with this article.
This article has loads of valuable and relevant information about mammal and human Treg biochemistry, and the relationship to PD.
I didn't post this because I think it's necessarily going to be the next "cure of the month".
I posted it because, along with a few other articles, it's helping me develop an understanding of Parkinson's disease etiology. It can help us better understand what causes PD and how to slow neural death and degradation.
I will be posting a broader discussion about these Treg cell articles soon. But for now, let more say this.
I too have been skeptical of this mouse model of PD, and I think it is reasonable to be. However, this article is starting to convince me that it's closer to human PD than I thought. The number of overlapping elements is greater than I knew.
I've been thinking for a while now about getting some turquoise killifish since they may be a natural model of PD. It would be a fun hobby, anyway. Trouble is I am way behind in my housework and yardwork already. First thing I want to try (after I get the hang of rearing them) is alpha ketoglutarate. Lots of stuff to try - maybe d-mannose (it increases Treg function & fish have something sort of like Tregs).
Also would like to add - thanks for posting this and for using a very descriptive headline. I was able to determine immediately if I wanted to read the post or not. I find the best way to save myself time is to only read and comment on posts that interest me - the rest I just ignore.
“Vitamin D supplementation may increase Treg/CD3 ratios in both healthy individuals and patients with autoimmune disorders and may increase Treg function. There remains a need for further suitably powered clinical studies aimed at enhancing Treg numbers and/or function.“
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