Pittsburgh Institute of Brain Disorders and Recovery and Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
Nat Rev Neurol. 2018 Sep;14(9):559-568. doi: 10.1038/s41582-018-0028-5.
The healthy immune system has natural checkpoints that temper pernicious inflammation. Cells mediating these checkpoints include regulatory T cells, regulatory B cells, regulatory dendritic cells, microglia, macrophages and monocytes. Here, we highlight discoveries on the beneficial functions of regulatory immune cells and their mechanisms of action and evaluate their potential use as novel cell-based therapies for brain disorders. Regulatory immune cell therapies have the potential not only to mitigate the exacerbation of brain injury by inflammation but also to promote an active post-injury brain repair programme. By harnessing the reparative properties of these cells, we can reduce over-reliance on medications that mask clinical symptoms but fail to impede or reverse the progression of brain disorders. Although these discoveries encourage further testing and genetic engineering of regulatory immune cells for the clinical management of neurological disorders, a number of challenges must be surmounted to improve their safety and efficacy in humans.
健康的免疫系统有天然的检查点来调节有害的炎症。介导这些检查点的细胞包括调节性 T 细胞、调节性 B 细胞、调节性树突状细胞、小胶质细胞、巨噬细胞和单核细胞。在这里,我们重点介绍了调节性免疫细胞的有益功能及其作用机制的发现,并评估了它们作为治疗脑疾病的新型基于细胞疗法的潜力。调节性免疫细胞疗法不仅有可能减轻炎症引起的脑损伤恶化,还有可能促进积极的损伤后脑修复计划。通过利用这些细胞的修复特性,我们可以减少对掩盖临床症状但不能阻止或逆转脑疾病进展的药物的过度依赖。尽管这些发现鼓励进一步测试和遗传工程调节性免疫细胞用于神经疾病的临床管理,但仍需克服许多挑战,以提高它们在人类中的安全性和有效性。