Holtman Inge R, Skola Dylan, Glass Christopher K
Department of Cellular and Molecular Medicine, UCSD, San Diego, California, USA.
Department of Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
J Clin Invest. 2017 Sep 1;127(9):3220-3229. doi: 10.1172/JCI90604. Epub 2017 Jul 31.
Microglia are the main resident macrophage population of the CNS and perform numerous functions required for CNS development, homeostasis, immunity, and repair. Many lines of evidence also indicate that dysregulation of microglia contributes to the pathogenesis of neurodegenerative and behavioral diseases. These observations provide a compelling argument to more clearly define the mechanisms that control microglia identity and function in health and disease. In this Review, we present a conceptual framework for how different classes of transcription factors interact to select and activate regulatory elements that control microglia development and their responses to internal and external signals. We then describe functions of specific transcription factors in normal and pathological contexts and conclude with a consideration of open questions to be addressed in the future.
小胶质细胞是中枢神经系统(CNS)主要的常驻巨噬细胞群体,执行着中枢神经系统发育、稳态、免疫和修复所需的众多功能。许多证据还表明,小胶质细胞的失调会导致神经退行性疾病和行为疾病的发病机制。这些观察结果为更清晰地定义在健康和疾病状态下控制小胶质细胞特性和功能的机制提供了有力论据。在本综述中,我们提出了一个概念框架,阐述了不同类别的转录因子如何相互作用,以选择和激活控制小胶质细胞发育及其对内部和外部信号反应的调控元件。然后,我们描述了特定转录因子在正常和病理情况下的功能,并最后考虑了未来需要解决的开放性问题。