| First Author | Trudler D | Year | 2020 |
| Journal | J Neurochem | Volume | 152 |
| Issue | 1 | Pages | 61-71 |
| PubMed ID | 31520492 | Mgi Jnum | J:282798 |
| Mgi Id | MGI:6383314 | Doi | 10.1111/jnc.14871 |
| Citation | Trudler D, et al. (2020) Alpha synuclein deficiency increases CD4(+) T-cells pro-inflammatory profile in a Nurr1-dependent manner. J Neurochem 152(1):61-71 |
| abstractText | It has been suggested that extracellular alpha synuclein (alphaSyn) can mediate neuroinflammation in Parkinson's disease, and that alphaSyn affects B-cell maturation. However, the function of alphaSyn in T cells is poorly understood. We hypothesized that alphaSyn can affect CD4(+) T-cell proliferation and activity. We found that alphaSyn deficiency exacerbates disease progression in 8 weeks old C57BL6/J EAE-induced mice, and that alphaSyn-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 alphaSyn on a background of alphaSyn 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 alphaSyn-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 alphaSyn-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. |
