Interleukin-33 promotes dopaminergic neuron survival and inhibits glial activation in Parkinson's disease models.

Interleukin-33 (IL33) plays a critical role in modulating immune and inflammatory responses across various diseases, yet its influence on Parkinson's disease (PD) remains elusive. In this study, we provide substantial evidence that global depletion of Il33 exacerbates PD pathology and motor deficits in vivo. Moreover, Il33 deficiency diminishes the communication between astrocytes and microglia, leading to a more profound injury to primary neurons in vitro. Notably, the application of recombinant IL33 (rIL33) following MPTP treatment or α-synucleinA53T overexpression partially inhibits the reduction in TH expression, glial activation, and the motor dysfunctions in vivo. Collectively, our findings demonstrate the opposed effects of Il33 deletion and rIL33 administration on neuroinflammation in PD, emphasizing the therapeutic potential of IL33 in regulating neuroinflammation and neuronal viability in the central nervous system (CNS).