Department of Physiology and Pharmacology, University of Georgia College of Veterinary Medicine, Athens, GA, 30602, USA.
Exp Mol Med. 2020 Sep;52(9):1517-1525. doi: 10.1038/s12276-020-00505-7. Epub 2020 Sep 24.
Numerous lines of evidence indicate an association between sustained inflammation and Parkinson's disease, but whether increased inflammation is a cause or consequence of Parkinson's disease remains highly contested. Extensive efforts have been made to characterize microglial function in Parkinson's disease, but the role of peripheral immune cells is less understood. Natural killer cells are innate effector lymphocytes that primarily target and kill malignant cells. Recent scientific discoveries have unveiled numerous novel functions of natural killer cells, such as resolving inflammation, forming immunological memory, and modulating antigen-presenting cell function. Furthermore, natural killer cells are capable of homing to the central nervous system in neurological disorders that exhibit exacerbated inflammation and inhibit hyperactivated microglia. Recently, a study demonstrated that natural killer cells scavenge alpha-synuclein aggregates, the primary component of Lewy bodies, and systemic depletion of natural killer cells results in exacerbated neuropathology in a mouse model of alpha-synucleinopathy, making them a highly relevant cell type in Parkinson's disease. However, the exact role of natural killer cells in Parkinson's disease remains elusive. In this review, we introduce the systemic inflammatory process seen in Parkinson's disease, with a particular focus on the direct and indirect modulatory capacity of natural killer cells in the context of Parkinson's disease.
大量证据表明，持续的炎症与帕金森病之间存在关联，但炎症增加是帕金森病的原因还是结果仍存在很大争议。人们已经做出了大量努力来描述帕金森病中的小胶质细胞功能，但外周免疫细胞的作用还不太清楚。自然杀伤细胞是先天效应淋巴细胞，主要靶向并杀死恶性细胞。最近的科学发现揭示了自然杀伤细胞的许多新功能，如缓解炎症、形成免疫记忆和调节抗原呈递细胞功能。此外，自然杀伤细胞能够归巢到中枢神经系统，在炎症加剧和抑制过度激活的小胶质细胞的神经退行性疾病中发挥作用。最近的一项研究表明，自然杀伤细胞清除α-突触核蛋白聚集体，即路易体的主要成分，而系统性耗尽自然杀伤细胞会导致α-突触核蛋白病小鼠模型中的神经病理学加重，这使得它们成为帕金森病中高度相关的细胞类型。然而，自然杀伤细胞在帕金森病中的确切作用仍不清楚。在这篇综述中，我们介绍了帕金森病中所见的系统性炎症过程，并特别关注了自然杀伤细胞在帕金森病背景下的直接和间接调节能力。
