Alpha synuclein deficiency increases CD4+ T-cells pro-inflammatory profile in a Nurr1-dependent manner

Dorit Trudler, Hilit Levy-Barazany, Yuval Nash, Liron Samuel, Ronit Sharon, Dan Frenkel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


It has been suggested that extracellular alpha synuclein (αSyn) can mediate neuroinflammation in Parkinson’s disease, and that αSyn affects B-cell maturation. However, the function of αSyn in T cells is poorly understood. We hypothesized that αSyn can affect CD4+ T-cell proliferation and activity. We found that αSyn deficiency exacerbates disease progression in 8 weeks old C57BL6/J EAE-induced mice, and that αSyn-deficient CD4+ T cells have increased pro-inflammatory response to myelin antigen relative to wild-type cells, as measured by cytokine secretion of interleukin IL-17 and interferon gamma. Furthermore, expression of αSyn on a background of αSyn knockout mitigates the inflammatory responses in CD4+ T cells. We discovered that elevated levels of Nurr1, a transcription factor belonging to the orphan nuclear receptor family, are associated with the pro-inflammatory profile of αSyn-deficient CD4+ T cells. In addition, we demonstrated that silencing of Nurr1 expression using an siRNA reduces IL-17 levels and increases the levels of IL-10, an anti-inflammatory cytokine. Study of αSyn-mediated cellular pathways in CD4+ T cells may provide useful insights into the development of pro-inflammatory responses in immunity, providing future avenues for therapeutic intervention. (Figure presented.).

Original languageAmerican English
Pages (from-to)61-71
Number of pages11
JournalJournal of Neurochemistry
Issue number1
StatePublished - 1 Jan 2020

Bibliographical note

Publisher Copyright:
© 2019 International Society for Neurochemistry


  • CD4 + T cells
  • Nurr1
  • alpha synuclein
  • multiple sclerosis


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