Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
Nat Immunol. 2018 Oct;19(10):1048-1058. doi: 10.1038/s41590-018-0212-1. Epub 2018 Sep 24.
The predominant type of immune cell in the brain is the microglia, a type of tissue-resident macrophage. In a variety of neurodegenerative settings, microglia alter their transcriptional profile, morphology and function in similar ways; thus, these activated cells have been called 'degeneration- or disease-associated microglia' (DAM). These activated microglia can perform different functions and exert both positive effects and negative effects in different mouse disease models. In humans, mutations in genes expressed in microglia are linked to various neurodegenerative diseases. Here we provide an overview of the common microglial response to neurodegeneration and key contributing pathways; delineate the multifaceted functions of activated microglia spanning various diseases; and discuss insights from the study of human disease-associated genes. We argue that strong evidence from both mouse models and human genetics causally links the function of activated microglia to neurodegeneration.
大脑中主要的免疫细胞是小胶质细胞，一种组织驻留巨噬细胞。在多种神经退行性疾病中，小胶质细胞以相似的方式改变其转录谱、形态和功能；因此，这些激活的细胞被称为“与变性或疾病相关的小胶质细胞”（DAM）。这些激活的小胶质细胞可以执行不同的功能，并在不同的小鼠疾病模型中产生积极和消极的影响。在人类中，小胶质细胞表达的基因突变与各种神经退行性疾病有关。在这里，我们提供了对神经退行性变中小胶质细胞常见反应以及关键贡献途径的概述；阐述了激活的小胶质细胞在各种疾病中的多方面功能；并讨论了人类疾病相关基因研究的新见解。我们认为，来自小鼠模型和人类遗传学的强有力证据表明，激活的小胶质细胞的功能与神经退行性变密切相关。
