Heterogeneity of microglia and their differential roles in white matter pathology
Heterogeneity of microglia and their differential roles in white matter pathology
复制标题
DOI：
10.1111/cns.13266
复制
发表时间：
2019-11-15
影响因子：
5.5
通讯作者：
Arai, Ken
中科院分区：
文献类型：
--
作者：
Lee, Janice;Hamanaka, Gen;Arai, Ken
小胶质细胞是在中枢神经系统（CNS）发育和疾病中发挥多种作用的常驻免疫细胞。虽然小胶质细胞/巨噬细胞活化的经典概念是基于双相的有害与有害极化，越来越多的证据表明，小胶质细胞活化的异质性更强，这是它们在CNS中复杂作用的基础。迄今为止，大多数数据都集中在灰质中的小胶质细胞上。然而，脱髓鞘是广泛疾病中的突出病理学发现，包括多发性硬化、阿尔茨海默病和血管性认知障碍和痴呆。在这篇简短的综述中，我们讨论了新发现的小胶质细胞的功能亚群，这些亚群在中枢神经系统疾病的发作和进展中对白色物质反应起作用。小胶质细胞根据疾病类型和大脑区域（尤其是在白色物质中）表现出不同的分子模式和形态。此外，在疾病的后期阶段，小胶质细胞表现出非常规的免疫调节活性，例如髓磷脂碎片的吞噬作用增加和刺激少突胶质细胞谱系细胞以促进髓鞘再生和疾病消退的营养因子的分泌。对这些多个小胶质细胞亚群的进一步研究可能会导致新的治疗方法来治疗CNS损伤和疾病中的白色物质病理。
Microglia are resident immune cells that play multiple roles in central nervous system (CNS) development and disease. Although the classical concept of microglia/macrophage activation is based on a biphasic beneficial-versus-deleterious polarization, growing evidence now suggests a much more heterogenous profile of microglial activation that underlie their complex roles in the CNS. To date, the majority of data are focused on microglia in gray matter. However, demyelination is a prominent pathologic finding in a wide range of diseases including multiple sclerosis, Alzheimer's disease, and vascular cognitive impairment and dementia. In this mini-review, we discuss newly discovered functional subsets of microglia that contribute to white matter response in CNS disease onset and progression. Microglia show different molecular patterns and morphologies depending on disease type and brain region, especially in white matter. Moreover, in later stages of disease, microglia demonstrate unconventional immuno-regulatory activities such as increased phagocytosis of myelin debris and secretion of trophic factors that stimulate oligodendrocyte lineage cells to facilitate remyelination and disease resolution. Further investigations of these multiple microglia subsets may lead to novel therapeutic approaches to treat white matter pathology in CNS injury and disease.