Citation

Increasing evidence suggests that Parkinson’s disease is an autoimmune disorder, with findings of elevated peripheral blood mononuclear cell in patients, and antigenic properties of ?-synuclein driving both the innate and adaptive immunity. Yet, how the interaction of ?-synuclein and a specific immune response participates to Parkinson’s disease ontogenesis has remained unanswered. Here, we reveal that autoimmune response to an ?-synuclein antigen underlies Parkinson’s disease. We demonstrate that autoimmunity mediated by CD4+T cell activation with ?-synuclein ?-syn61-75antigen is required to lead to immune cell infiltration and localized inflammation in the substantia nigra, triggering dopaminergic cell neurodegeneration and deficits in locomotion and gait kinematics. This study offers the first immune-induced mouse model that recapitulates all features of Parkinson’s disease to study the mechanisms triggering disease onset. It provides the basis for temporally tracking symptom development, exploring preventive strategies and prodromal therapeutic interventions in Parkinson’s Disease.In briefPeripheral ?-synuclein immunization causes Parkinson’s disease-like symptoms in mice.Highlights- Both CD4+ T cells and ?-synuclein are essential for Parkinson’s disease ontogenesis.- Peripheral injection of ?-syn61-75induces significant CD4+ T cell infiltration in the mouse brain.- ?-syn61-75immunization is associated with inflammation, ?-synuclein aggregation and dopaminergic cell loss in the substantia nigra pars compacta.- Levodopa-sensitive motor symptoms are detected 8 weeks following ?-syn61-75immunization in mice.- This study offers a novel autoimmune ?-synuclein induced mouse model of Parkinson’s disease.