Autoimmune mechanisms implicated in Parkinson’s disease

Monocyte-derived dendritic cells from patients with Parkinson’s disease present a dysregulated cytokine profile. The subset of cytokines that is altered promotes T-cell polarisation towards autoimmune-related Th1/Th17 cells. The authors conclude that this data supports the hypothesis that autoimmune mechanisms may be implicated in Parkinson’s disease.

One of the major hallmarks of Parkinson’s disease is inflammation. Furthermore, the Parkinson’s disease-related genes PINK1 and Parkin regulate the mitochondrial antigen presentation pathway. PINK1 aggregates on damaged mitochondria and recruits Parkin, thus triggering mitophagy. If PINK1 or Parkin are missing, mitochondrial-derived vesicles (MDV) may form. The mitochondrial antigens contained within the MDVs may be expressed at the cell surface. To better understand the processes taking place in the periphery in Parkinson’s disease, Canadian researchers investigated whether antigen-presenting cells (APCs) from patients display a dysregulated cytokine expression profile [1]. Monocyte-derived dendritic cells were generated from peripheral blood mononuclear cells (PBMCs) of patients with Parkinson’s disease and healthy controls to characterise their cytokine expression profile after lipopolysaccharide (LPS) or bacterial (Enteropathogenic Escherichia coli [EPEC]) stimulation. The results were presented by Dr Camille Michaud (University of Montreal Hospital Research Centre, Canada).

The results demonstrated that inflammation and ageing regulate expression of PINK1 and Parkin. Treatment of inflammation induced by LPS/EPEC reduced the expression of PINK1 and Parkin. Loss of co-localisation between patients' monocyte-derived dendritic cells could indicate activation of the MDV/mitochondrial antigen presentation pathway. Monocyte-derived dendritic cells of patients with Parkinson’s disease produced more pro-inflammatory cytokines in response to LPS and EPEC.

1. Michaud C, et al. Antigen-presenting cells from PD patients exhibit an autoinflammatory cytokine profile. S27.001, AAN 2021 Virtual Congress, 17-22 April.

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Posted on 16 June, 2021