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α-Synuclein vaccination modulates regulatory T cell activation and microglia in the absence of brain pathology

Overview of attention for article published in Journal of Neuroinflammation, April 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • High Attention Score compared to outputs of the same age and source (89th percentile)

Mentioned by

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1 news outlet
twitter
4 tweeters

Citations

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26 Dimensions

Readers on

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59 Mendeley
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1 CiteULike
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Title
α-Synuclein vaccination modulates regulatory T cell activation and microglia in the absence of brain pathology
Published in
Journal of Neuroinflammation, April 2016
DOI 10.1186/s12974-016-0532-8
Pubmed ID
Authors

Josefine R. Christiansen, Mads N. Olesen, Daniel E. Otzen, Marina Romero-Ramos, Vanesa Sanchez-Guajardo

Abstract

Passive and active immunization with α-synuclein has been shown to be neuroprotective in animal models of Parkinson's disease. We have previously shown that vaccination with α-synuclein, long before α-synuclein-induced brain pathology, prevents striatal degeneration by inducing regulatory T cell infiltration in parenchyma and antibody deposition on α-synuclein overexpressing neurons. However, the effect of peripheral α-synuclein on the immune system is unknown, as are the mechanistic changes induced in the CD4 T cell population during successful neuroprotective animal studies. We have studied the changes induced by vaccination with α-synuclein in the CD4 T cell pool and its impact on brain microglia to understand the immune mechanisms behind successful vaccination strategies in Parkinson's disease animal models. Mice were immunized with WT or nitrated α-synuclein at a dose equivalent to the one used in our previous successful vaccination strategy and at a higher dose to determine potential dose-dependent effects. Animals were re-vaccinated 4 weeks after and sacrificed 5 days later. These studies were conducted in naive animals in the absence of human α-synuclein expression. The CD4 T cell response was modulated by α-synuclein in a dose-dependent manner, in particular the regulatory T cell population. Low-dose α-synuclein induced expansion of naive (Foxp3 + CCR6-CD127lo/neg) and dopamine receptor type D3+ regulatory T cells, as well as an increase in Stat5 protein levels. On the other hand, high dose promoted activation of regulatory T cells (Foxp3CCR6 + CD127lo/neg), which were dopamine receptor D2+D3-, and induced up-regulation of Stat5 and production of anti-α-synuclein antibodies. These effects were specific to the variant of α-synuclein used as the pathology-associated nitrated form induced distinct effects at both doses. The changes observed in the periphery after vaccination with low-dose α-synuclein correlated with an increase in CD154+, CD103+, and CD54+ microglia and the reduction of CD200R+ microglia. This resulted in the induction of a polarized tolerogenic microglia population that was CD200R-CD54CD103CD172a+ (82 % of total microglia). We have shown for the first time the mechanisms behind α-synuclein vaccination and, importantly, how we can modulate microglia's phenotype by regulating the CD4 T cell pool, thus shedding invaluable light on the design of neuroimmunoregulatory therapies for Parkinson's disease.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 59 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 14%
Student > Master 8 14%
Student > Ph. D. Student 6 10%
Professor > Associate Professor 5 8%
Student > Bachelor 4 7%
Other 10 17%
Unknown 18 31%
Readers by discipline Count As %
Neuroscience 17 29%
Agricultural and Biological Sciences 8 14%
Biochemistry, Genetics and Molecular Biology 5 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Computer Science 2 3%
Other 6 10%
Unknown 19 32%

Attention Score in Context

This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 December 2016.
All research outputs
#982,363
of 11,220,852 outputs
Outputs from Journal of Neuroinflammation
#86
of 1,270 outputs
Outputs of similar age
#37,986
of 282,055 outputs
Outputs of similar age from Journal of Neuroinflammation
#6
of 58 outputs
Altmetric has tracked 11,220,852 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,270 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done particularly well, scoring higher than 92% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 282,055 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 58 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 89% of its contemporaries.