| Autor: |
Trudler, Dorit, Levy‐Barazany, Hilit, Nash, Yuval, Samuel, Liron, Sharon, Ronit, Frenkel, Dan |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; Jan2020, Vol. 152 Issue 1, p61-71, 11p |
| Abstrakt: |
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] |
| Databáze: |
Complementary Index |
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