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

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. [ABSTRACT FROM AUTHOR]