Laboratory of Neuroimmunology, Federal Center of Brain Research and Neurotechnologies of the Federal Medical-Biological Agency of Russia, 117513, Moscow, Russia.
Laboratory of Neuroimmunology, Federal Center of Brain Research and Neurotechnologies of the Federal Medical-Biological Agency of Russia, 117513, Moscow, Russia; Department of Neurology, Neurosurgery and Medical Genetics of Pirogov Russian National Research Medical University, 117997, Moscow, Russia; Laboratory of Clinical Immunology, National Research Center Institute of Immunology of the Federal Medical-Biological Agency, 115478, Moscow, Russia.
Int Immunopharmacol. 2024 Aug 20;137:112540. doi: 10.1016/j.intimp.2024.112540. Epub 2024 Jun 22.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with autoimmune mechanism of development. The investigation of neuroimmune interaction is one of the most developing directions in MS pathogenesis study. Catecholamines are direct mediators of this interaction and can be involved in the pathogenesis of MS by modulating cells of both innate and adaptive immune systems. The aim of this study was to investigate the influence of dopamine and norepinephrine on the ability of monocytes of patients with relapsing-remitting MS, to induce Th17- and Th1-immune response, which play a crucial role in the autoimmunity of the CNS. We found, that both dopamine and norepinephrine modulate the production of Th17- (IL-23, IL-1β, and IL-6) and Th1-promoting (IL-12p70) cytokines by activated peripheral blood mononuclear cells or CD14 monocytes in patients with MS and in healthy subjects. We also found the inhibitory effect of dopamine and norepinephrine on monocyte-induced production of IL-17 and IFN-γ by autologous CD4 T-cells in both groups. Finally, the multidirectional role of D- and D-like dopaminergic receptors in the modulatory effect of dopamine on the ability of CD14 monocytes to activate CD4 T-cells was established, expanding the potential role of dopamine in the neuroimmune interaction.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性脱髓鞘疾病，其发病机制具有自身免疫性。神经免疫相互作用的研究是 MS 发病机制研究中最具发展前景的方向之一。儿茶酚胺是这种相互作用的直接介质，通过调节先天和适应性免疫系统的细胞，可参与 MS 的发病机制。本研究旨在探讨多巴胺和去甲肾上腺素对复发缓解型 MS 患者单核细胞诱导 Th17 和 Th1 免疫反应能力的影响，Th17 和 Th1 免疫反应在 CNS 自身免疫中起着至关重要的作用。我们发现，多巴胺和去甲肾上腺素均可调节 MS 患者和健康受试者外周血单个核细胞或 CD14 单核细胞激活后产生 Th17 （IL-23、IL-1β和 IL-6）和 Th1 促进（IL-12p70）细胞因子的能力。我们还发现，多巴胺和去甲肾上腺素对两组患者单核细胞诱导的自身 CD4 T 细胞产生 IL-17 和 IFN-γ的抑制作用。最后，确定了 D-和 D 样多巴胺能受体在多巴胺对 CD14 单核细胞激活 CD4 T 细胞能力的调节作用中的多向作用，扩展了多巴胺在神经免疫相互作用中的潜在作用。
