IL-2/anti-IL-2 complexes attenuates neuroinflammation and neurodegeneration in mice of experimental Parkinson's disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease, with motor and non-motor symptoms being its main clinical manifestations. Neuroinflammation has been shown to involve in pathogenesis of PD. Regulatory T cells (Tregs) in PD exhibited reduction in number and suppressive activity. Existing methods to increase the Tregs remains challenging for clinical application because of the difficulty in Tregs expanding or serious side-effects. Therefore, new approaches still need to be explored to balance the amount and activity of Tregs. In this study, we assessed the protective effects of IL-2/anti-IL-2 complexes (IL-2C) on mouse models of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). And the results showed that IL-2C significantly increased the number of Tregs both in spleen and brain, accompanied by reduced nigral dopaminergic neuron loss and behavioral defects. Besides, IL-2C also attenuated neuroinflammation as observed by diminished glial activation, fewer infiltration of CD4⁺ and CD8⁺ T cells and reduced pro-inflammatory cytokines releasing in the nigral region. Moreover, the protective effects of IL-2C were abolished by pre-treatment of anti-CD25 antibody (PC61), which was used to delete the Tregs. In summary, our results demonstrate that IL-2C-induced Tregs expansion attenuates the dopaminergic neurons loss and the neuroinflammatory response in vivo, suggesting that IL-2C maybe a promising therapeutic target for PD.