Elevated levels of pro-inflammatory cytokines have been shown in the serum of PD patients and mouse models suggesting that peripherally occurring inflammatory processes participate in PD pathogenesis.  Changes in levels of cytokines may have major impacts on T cell polarization, a feature that has been observed in PD patients’ blood. However, the cells responsible for this dysregulated production of cytokines, their exact expression profile and the consequences on T cell polarization remain unknown. Furthermore, PINK1, a PD-related gene, represses pro-inflammatory cytokine production mediated by the cGAS/STING pathway (an innate immune signaling pathway that detects cytosolic DNA). PINK1 is also a major repressor of mitochondrial antigen presentation (MitAP). MitAP depends on mitochondrial-derived vesicle (MDV) formation and is involved in mitochondrial autoimmune responses and in PD pathogenesis. We hypothesize that APCs are cells presenting a dysregulated cytokine profile in PD that skew T cell polarization.

Monocyte-derived dendritic cells (MDDCs) from PD patients and sex/age matched healthy individuals were generated from PBMCs to characterize their cytokine expression profile after LPS or bacterial stimulation using RT-qPCR and multiplex immunoassays.

We report that MDDCs from PD patients present a dysregulated cytokine profile. Moreover, only  a subset of cytokines is altered which promotes the T cell polarization towards autoimmune-related Th17 cells.

Our results indicate that the dysregulated inflammation observed in PD patients affects APCs by inducing the production of pro-Th17 cytokines. These data strongly support the hypothesis that autoimmune mechanisms are implicated in PD. This project should allow us to better understand the role of autoimmunity in PD and to identify new biomarkers.