Dopaminergic Receptors on CD4+ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson's Disease.
Dopaminergic Receptors on CD4+ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson's Disease.
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DOI：
10.1038/srep33738
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发表时间：
2016-09-22
影响因子：
4.6
通讯作者：
Cosentino M
中科院分区：
文献类型：
--
作者：
Kustrimovic N;Rasini E;Legnaro M;Bombelli R;Aleksic I;Blandini F;Comi C;Mauri M;Minafra B;Riboldazzi G;Sanchez-Guajardo V;Marino F;Cosentino M
帕金森病（PD）的特征是黑质致密部多巴胺能神经元缺失、富含α-突触核蛋白（α-syn）的神经元内包涵体（路易体）和小胶质细胞激活。新的证据表明，CD4+ T淋巴细胞参与PD的神经炎症。由于帕金森病的治疗主要是多巴胺能替代疗法，多巴胺是一种连接神经和免疫系统的既定递质，我们检测了PD患者和健康受试者（HS）的CD4+ T naive和记忆淋巴细胞，特别关注多巴胺能受体（DR）的表达。此外，还观察α-syn对CD4+ T初始细胞和记忆细胞的体外作用。UPDRS第三部分评分显示，T淋巴细胞中DR表达与运动功能障碍之间存在广泛关联。在总T细胞和CD4+ T幼稚细胞中，d1样DR表达降低，而在T记忆细胞中，d2样DR表达随评分升高而升高。α-syn在体外增加PD患者和HS患者CD4+ T记忆细胞的程度可能不同，并以细胞亚群特异性模式影响DR的表达。本研究结果支持外周适应性免疫参与帕金森病，并可能有助于开发新的帕金森病免疫疗法，以及更好地利用现有的多巴胺能抗帕金森药物。
Parkinson’s disease (PD) is characterized by loss of dopaminergic neurons in substantia nigra pars compacta, α-synuclein (α-syn)-rich intraneuronal inclusions (Lewy bodies), and microglial activation. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is dopaminergic substitution therapy and dopamine is an established transmitter connecting nervous and immune systems, we examined CD4+ T naive and memory lymphocytes in PD patients and in healthy subjects (HS), with specific regard to dopaminergic receptor (DR) expression. In addition, the in vitro effects of α-syn were assessed on CD4+ T naive and memory cells. Results showed extensive association between DR expression in T lymphocytes and motor dysfunction, as assessed by UPDRS Part III score. In total and CD4+ T naive cells expression of D1-like DR decrease, while in T memory cells D2-like DR increase with increasing score. In vitro, α-syn increased CD4+ T memory cells, possibly to a different extent in PD patients and in HS, and affected DR expression with cell subset-specific patterns. The present results support the involvement of peripheral adaptive immunity in PD, and may contribute to develop novel immunotherapies for PD, as well as to better use of current dopaminergic antiparkinson drugs.
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影响因子：
82.9
作者：
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