Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system in which the immune system plays a central role. In particular, effector populations such as T helper (Th) 1, Th9, Th17, and Th22 cells are involved in disease development, whereas T regulatory cells (Tregs) are associated with the resolution of the disease. Melatonin levels are impaired in patients with MS, and exogenous melatonin ameliorates the disease in MS animal models by modulating the Th1/Th17/Treg responses and also improves quality of life and several symptoms in patients with MS. However, no study has examined melatonin's effect on T cells from relapsing‐remitting MS (RR‐MS) patients. Therefore, the objectives of the present study were to evaluate the effects of the in vitro administration of melatonin to peripheral blood mononuclear cells (PBMCs) from 64 RR‐MS patients and 64 sex‐ and age‐matched healthy subjects on Th1, Th9, Th17, Th22, and Treg responses and to analyze the expression of the melatonin effector/receptor system in these cells. Melatonin decreased Th1 and Th22 responses in patients, whereas it did not affect the Th17 and Treg subsets. Melatonin also promoted skewing toward a more protective cytokine microenvironment, as shown by an increased anti‐inflammatory/Th1 ratio. Furthermore, for the first time, we describe the overexpression of the melatonin effector/receptor system in PBMCs from patients with MS; this alteration might be relevant to the disease because acetylserotonin O‐methyltransferase expression significantly correlates with disease progression and T effector/regulatory responses in patients. Therefore, our data suggest that melatonin may be an effective treatment for MS.

中文翻译：

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褪黑素减少复发性多发性硬化症患者外周T辅助淋巴细胞的炎症反应

多发性硬化症（MS）是中枢神经系统的神经炎性疾病，其中免疫系统起着核心作用。特别地，诸如T辅助细胞（Th），Th9，Th17和Th22细胞的效应子群体参与疾病发展，而T调节细胞（Tregs）与疾病的解决有关。MS患者褪黑激素水平受损，外源性褪黑激素可通过调节Th1 / Th17 / Treg反应改善MS动物模型的疾病，并改善MS患者的生活质量和多种症状。但是，尚无研究研究褪黑激素对复发缓解型MS（RR-MS）患者T细胞的影响。所以，本研究的目的是评估褪黑激素对64名RR‐MS患者和64名性别和年龄匹配的健康受试者的外周血单核细胞（PBMC）的体外治疗对Th1，Th9，Th17，Th22的影响，以及Treg反应，并分析褪黑激素效应器/受体系统在这些细胞中的表达。褪黑激素降低了患者的Th1和Th22反应，而它并不影响Th17和Treg亚群。褪黑激素还促进了偏向更具保护性的细胞因子微环境的偏斜，如增加的抗炎/ Th1比率所示。此外，我们首次描述了MS患者的PBMC中褪黑激素效应/受体系统的过表达。这种改变可能与疾病有关，因为乙酰5-羟色胺O-甲基转移酶的表达与患者的疾病进展和T效应/调节反应显着相关。因此，我们的数据表明褪黑激素可能是MS的有效治疗方法。