The role of Th17 cells in the pathogenesis of Parkinson's disease: From immune dysregulation to neurodegeneration.

Parkinson's disease (PD) is a neurological disorder with the fastest global growth rate, marked by the deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of α-synuclein (α-syn) deposits in neuronal cells. This progressive neurodegenerative disorder impacts both peripheral organs and the central nervous system (CNS), with neuroinflammation playing a pivotal role in its pathophysiological mechanisms. Research indicates that the adaptive immune response, particularly neuroinflammation mediated by T helper 17 (Th17) cells, a subset of CD4⁺ T cells characterized primarily by their secretion of interleukin-17 (IL-17), is strongly implicated in the pathological process of PD. Despite significant recent advances in mechanistic and translational research, a comprehensive synthesis integrating Th17 activation mechanisms, pathogenic crosstalk with other immune subsets, and the resultant Th17/Treg imbalance is currently lacking, thereby hindering the translation of immunological findings into targeted therapeutic interventions. This review considers in detail the mechanistic roles of Th17 cells in PD, including their activation mechanisms, pathogenic pathways, crosstalk with other immune cell subsets, and immune dysregulation with Tregs. Our analysis aims to offer an integrated perspective on the immunological mechanisms underlying Th17 cells in PD, thereby facilitating a deeper comprehension of disease pathogenesis and guiding the development of future immune-based therapeutic strategies.