McFleder Rhonda L, Musacchio Thomas, Keller Johanna, Knorr Susanne, Petschner Tobias, Chen Jia Zhi, Muthuraman Muthuraman, Badr Mohammad, Harder-Rauschenberger Lisa, Kremer Fabian, Asci Selin, Steinhauser Sophie, Karl Ann-Kathrin, Brotchie Jonathan M, Koprich James B, Volkmann Jens, Ip Chi Wang
Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.
Atuka Inc., Toronto, ON, Canada; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
Brain Behav Immun. 2025 Jan;123:851-862. doi: 10.1016/j.bbi.2024.10.039. Epub 2024 Oct 29.
Immune dysregulation in the brain and periphery is thought to contribute to the detrimental neurodegeneration that occurs in Parkinson's disease (PD). Identifying mechanisms to reverse this dysregulation is key to developing disease-altering therapeutics for this currently incurable disease. Here we utilized the longitudinal data from the Parkinson's Progression Marker Initiative to demonstrate that circulating lymphocytes progressively decline in PD and can be used to predict future motor symptom progression. Deep brain stimulation (DBS), which is used as a symptomatic treatment, could halt this progressive decline. By analyzing specific immune populations from a second cohort of patients, we could show that DBS causes a shift from the pro-inflammatory CD4 T helper 17 cells driving neurodegeneration to anti-inflammatory CD4 regulatory T cells. RNA-sequencing and immunohistochemistry in the brain of the A53T alpha-synuclein rat model of PD revealed that DBS also decreases neuroinflammation. These data suggest a potential disease-altering role for DBS by halting inflammatory processes.
大脑和外周的免疫失调被认为是导致帕金森病（PD）中有害神经退行性变的原因。确定逆转这种失调的机制是开发针对这种目前无法治愈疾病的改变疾病疗法的关键。在这里，我们利用帕金森病进展标志物倡议的纵向数据来证明，循环淋巴细胞在PD中会逐渐减少，并且可用于预测未来运动症状的进展。作为对症治疗手段的深部脑刺激（DBS）可以阻止这种渐进性下降。通过分析第二批患者的特定免疫群体，我们可以表明DBS会导致驱动神经退行性变的促炎性CD4辅助性T细胞17向抗炎性CD4调节性T细胞转变。在PD的A53Tα-突触核蛋白大鼠模型的大脑中进行的RNA测序和免疫组织化学显示，DBS还可减轻神经炎症。这些数据表明DBS通过阻止炎症过程可能具有改变疾病的作用。
