Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario K7L 3N6, Canada.
J Neuroimmunol. 2019 Jun 15;331:28-35. doi: 10.1016/j.jneuroim.2018.03.006. Epub 2018 Mar 13.
Remyelination following myelin/oligodendrocyte injury in the central nervous system (CNS) is dependent on oligodendrocyte progenitor cells (OPCs) migrating into lesion sites, differentiating into myelinating oligodendrocytes (OLs), and ensheathing axons. Experimental models indicate that robust OPC-dependent remyelination can occur in the CNS; in contrast, histologic and imaging studies of lesions in the human disease multiple sclerosis (MS) indicate the variable extent of this response, which is particularly limited in more chronic MS lesions. Immune-mediated mechanisms can contribute either positively or negatively to the presence and functional responses of OPCs. This review addresses i) the molecular signature and functional properties of OPCs in the adult human brain; ii) the status (presence and function) of OPCs in MS lesions; iii) experimental models and in vitro data highlighting the contribution of adaptive and innate immune constituents to OPC injury and remyelination; and iv) effects of MS-directed immunotherapies on OPCs, either directly or indirectly via effects on specific immune constituents.
中枢神经系统(CNS)髓鞘/少突胶质细胞损伤后的髓鞘再生依赖于少突胶质前体细胞(OPC)迁移到病变部位,分化为髓鞘形成的少突胶质细胞(OL),并包裹轴突。实验模型表明,CNS 中可以发生强大的 OPC 依赖性髓鞘再生;相比之下,对多发性硬化症(MS)人类疾病病变的组织学和影像学研究表明,这种反应的程度存在差异,在更慢性的 MS 病变中尤其有限。免疫介导的机制可以对 OPC 的存在和功能反应产生积极或消极的影响。这篇综述讨论了:i)成人大脑中 OPC 的分子特征和功能特性;ii)MS 病变中 OPC 的状态(存在和功能);iii)强调适应性和先天免疫成分对 OPC 损伤和髓鞘再生贡献的实验模型和体外数据;iv)MS 靶向免疫疗法对 OPC 的影响,无论是直接还是间接通过对特定免疫成分的影响。