Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, No. 1 Eastern Jian-she Road, Zhengzhou, 450052, Henan, China.
The Academy of Medical Sciences of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
J Neurol. 2022 Dec;269(12):6386-6394. doi: 10.1007/s00415-022-11258-w. Epub 2022 Jul 27.
Mounting evidence indicates the involvement of the innate immune system in Parkinson's disease (PD). Nevertheless, the implications of peripheral monocytes have not been fully elucidated. Although alpha-synuclein (α-synuclein) has been described as a pathological hallmark of PD, the proinflammatory effect of α-synuclein on monocytes is understudied. This study aimed to comprehensively characterize peripheral monocytes in PD patients and to investigate the proinflammatory magnitude of fibrillar α-synuclein.
Using flow cytometry, we explored the distribution of monocytic subpopulations. We also investigated the actions of peripheral monocytes in response to lipopolysaccharides (LPS) and to fibrillar α-synuclein stimuli by measuring inflammatory molecule levels in post-culture supernatants.
Classical monocytes were enriched, in parallel with lower proportions of intermediate and nonclassical monocytes in patients with PD than in controls. Lower levels of TNF-α and IL-6 were spontaneously produced by unstimulated monocytes in patients with PD. LPS and fibrillar α-synuclein stimuli induced high levels of TNF-α, IL-1β, IL-6, and sCD163 in the PD and control groups. Strikingly, the fold induction of TNF-α and IL-6 was lower in patients with PD than that in normal controls under the same stimulation.
Our results revealed a strong dysregulation of peripheral monocytes in PD patients, including subpopulation shifts and impaired response to specific stimuli, and the proinflammatory effect of α-synuclein on monocytes. Further studies are needed to clarify the specific mechanisms by which these immunological abnormalities are present in PD to open the possibility of immunoregulatory therapy.
越来越多的证据表明，固有免疫系统参与了帕金森病（PD）的发生。然而，外周单核细胞的作用尚未完全阐明。尽管α-突触核蛋白（α-synuclein，α-syn）已被描述为 PD 的病理标志，但α-syn 对单核细胞的促炎作用仍研究不足。本研究旨在全面描述 PD 患者外周血单核细胞，并研究纤维状α-syn 对单核细胞的促炎作用。
我们使用流式细胞术研究了单核细胞亚群的分布。我们还通过测量培养后上清液中炎症分子的水平，研究了外周单核细胞对脂多糖（LPS）和纤维状α-syn 刺激的反应。
与对照组相比，PD 患者的经典单核细胞增多，中间和非经典单核细胞比例降低。PD 患者未刺激的单核细胞自发产生的 TNF-α 和 IL-6 水平较低。LPS 和纤维状α-syn 刺激在 PD 组和对照组中诱导产生高水平的 TNF-α、IL-1β、IL-6 和 sCD163。引人注目的是，在相同刺激下，PD 患者的 TNF-α 和 IL-6 的诱导倍数低于正常对照组。
我们的研究结果揭示了 PD 患者外周血单核细胞存在强烈的失调，包括亚群转移和对特定刺激的反应受损，以及α-syn 对单核细胞的促炎作用。需要进一步研究以阐明 PD 中存在这些免疫异常的具体机制，为免疫调节治疗开辟可能性。
