Alpha synuclein deficiency increases CD4+ T-cells pro-inflammatory profile in a Nurr1-dependent manner.
J Neurochem
; 152(1): 61-71, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31520492
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
/
Linfocitos T CD4-Positivos
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Encefalomielitis Autoinmune Experimental
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Alfa-Sinucleína
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Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2020
Tipo del documento:
Article
País de afiliación:
Israel