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[多巴胺作为树突状细胞与T细胞之间的免疫调节剂及多巴胺在类风湿关节炎发病机制中的作用]

[Dopamine as an immune-modulator between dendritic cells and T cells and the role of dopamine in the pathogenesis of rheumatoid arthritis].

作者信息

Nakano Kazuhisa, Matsushita Sho, Saito Kazuyoshi, Yamaoka Kunihiro, Tanaka Yoshiya

机构信息

The first dept. of Internal Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan.

出版信息

Nihon Rinsho Meneki Gakkai Kaishi. 2009 Feb;32(1):1-6. doi: 10.2177/jsci.32.1.

Abstract

The nerve systems affect immune functions by releasing neurotransmitters through lymphocyte cell-surface receptors. A major neurotransmitter dopamine transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. There is wide evidence for a decreased risk of rheumatoid arthritis (RA) in patients with schizophrenia which is associated with the excessive stimulation of D2-like receptors by dopamine. However, the reason for the negative association between RA and schizophrenia is unknown. We previously demonstrated that dendritic cells (DCs) could synthesize and store dopamine, DC released dopamine to naive CD4 T cells upon DC-T cell interaction and affected helper T-cell differentiation. Because DCs have been proposed to play a pivotal role in the initiation and perpetuation of RA by presentation of arthritogenic antigens to T cells, we here assessed effects and functions of dopamine on immune cells during the pathogenesis of RA. In this paper, we overview the series of our research findings, and present the possibility of drug discovery which target at dopamine receptors.

摘要

神经系统通过淋巴细胞表面受体释放神经递质来影响免疫功能。一种主要的神经递质多巴胺通过五种不同的七跨膜G蛋白偶联受体(称为D1至D5)传递信号。有充分证据表明,精神分裂症患者患类风湿性关节炎(RA)的风险降低,这与多巴胺对D2样受体的过度刺激有关。然而,RA与精神分裂症之间负相关的原因尚不清楚。我们之前证明,树突状细胞(DCs)可以合成并储存多巴胺,DC与幼稚CD4 T细胞相互作用时会将多巴胺释放到这些细胞中,并影响辅助性T细胞的分化。由于DCs被认为通过向T细胞呈递致关节炎抗原来在RA的起始和持续过程中起关键作用,因此我们在此评估了多巴胺在RA发病机制中对免疫细胞的影响和功能。在本文中,我们概述了我们的一系列研究发现,并提出了以多巴胺受体为靶点的药物发现的可能性。

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