Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses.
Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses.
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DOI：
10.1016/j.cell.2015.08.025
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发表时间：
2015-09-10
期刊：
影响因子：
64.5
通讯作者：
Correale J
中科院分区：
文献类型：
--
作者：
Farez MF;Mascanfroni ID;Méndez-Huergo SP;Yeste A;Murugaiyan G;Garo LP;Balbuena Aguirre ME;Patel B;Ysrraelit MC;Zhu C;Kuchroo VK;Rabinovich GA;Quintana FJ;Correale J
多发性硬化症是一种影响中枢神经系统的自身免疫性疾病，在多发性硬化症中观察到了疾病活动的季节性变化。这些流行病学观察结果表明，环境因素影响疾病的进程。在这里，我们报告说，褪黑激素水平，其生产是由夜间长度的季节性变化调制，与人类多发性硬化症的活动呈负相关。在多发性硬化症的实验模型中，用褪黑激素治疗可以改善疾病，并直接干扰人类和小鼠T细胞的分化。褪黑激素诱导阻遏转录因子Nfil 3的表达，阻断致病性Th 17细胞的分化，并通过Erk 1/2和ROR-α对IL-10启动子的反式激活促进保护性Tr 1细胞的产生。这些结果表明，褪黑激素是环境驱动的线索如何影响T细胞分化的另一个例子，并对多发性硬化等自身免疫性疾病有影响。
Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the central nervous system. These epidemiological observations suggest that environmental factors influence the disease course. Here we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells as well as boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact on T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.