Neuroscience Laboratory, CHU of Quebec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Boul., Quebec City, QC, G1V 4G2, Canada.
Laboratory of Innate Immunity, CHU of Quebec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier Boul., Quebec City, QC, G1V 4G2, Canada.
Neurotherapeutics. 2021 Apr;18(2):889-904. doi: 10.1007/s13311-020-00998-0. Epub 2021 Jan 21.
The significance of monocytes has been demonstrated in multiple sclerosis (MS). One of the therapeutic challenges is developing medications that induce mild immunomodulation that is solely targeting specific monocyte subsets without affecting microglia. Muramyl dipeptide (MDP) activates the NOD2 receptor, and systemic MDP administrations convert Ly6C into Ly6C monocytes. Here, we report selective immunomodulatory and therapeutic effects of MDP on cuprizone and experimental autoimmune encephalomyelitis (EAE) mouse models of MS. MDP treatment exerted various therapeutic effects in EAE, including delaying EAE onset and reducing infiltration of leukocytes into the CNS before EAE onset. Of great interest is the robust beneficial effect of the MDP treatment in mice already developing the disease several days after EAE onset. Finally, we found that the NOD2 receptor plays a critical role in MDP-mediated EAE resistance. Our results demonstrate that MDP is beneficial in both early and progressive phases of EAE. Based on these results, and upon comprehensive basic and clinical research, we anticipate developing NOD2 agonist-based medications for MS in the future.
单核细胞在多发性硬化症（MS）中具有重要意义。治疗上的一个挑战是开发药物，诱导轻度免疫调节，仅针对特定单核细胞亚群，而不影响小胶质细胞。肽聚糖二肽（MDP）激活 NOD2 受体，全身给予 MDP 将 Ly6C 转化为 Ly6C 单核细胞。在这里，我们报告 MDP 对杯状朊病毒和实验性自身免疫性脑脊髓炎（EAE）多发性硬化症小鼠模型的选择性免疫调节和治疗作用。MDP 治疗在 EAE 中发挥了多种治疗作用，包括在 EAE 发作前延迟 EAE 发作并减少白细胞浸润中枢神经系统。有趣的是，在 EAE 发作几天后已经发病的小鼠中，MDP 治疗具有强大的有益作用。最后，我们发现 NOD2 受体在 MDP 介导的 EAE 抵抗中起关键作用。我们的结果表明 MDP 对 EAE 的早期和进展阶段均有益。基于这些结果，并经过全面的基础和临床研究，我们预计未来将开发基于 NOD2 激动剂的多发性硬化症药物。
