Cheray Mathilde, Joseph Bertrand
Toxicology Unit, Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden.
Front Cell Neurosci. 2018 Aug 3;12:243. doi: 10.3389/fncel.2018.00243. eCollection 2018.
Microglia, resident immune cells of the central nervous system, fulfill multiple functions in the brain throughout life. These microglial functions range from participation in innate and adaptive immune responses, involvement in the development of the brain and its homeostasis maintenance, to contribution to degenerative, traumatic, and proliferative diseases; and take place in the developing, the aging, the healthy, or the diseased brain. Thus, an impressive level of cellular plasticity, appears as a requirement for the pleiotropic biological functions of microglia. Epigenetic changes, including histone modifications or DNA methylation as well as microRNA expression, are important modifiers of gene expression, and have been involved in cell phenotype regulation and reprogramming and are therefore part of the mechanisms regulating cellular plasticity. Here, we review and discuss the epigenetic mechanisms, which are emerging as contributors to this microglial cellular plasticity and thereby can constitute interesting targets to modulate microglia associated brain diseases, including developmental diseases, neurodegenerative diseases as well as cancer.
小胶质细胞是中枢神经系统的常驻免疫细胞,在整个生命过程中在大脑中发挥多种功能。这些小胶质细胞的功能范围从参与先天性和适应性免疫反应、参与大脑发育及其稳态维持,到促成退行性、创伤性和增殖性疾病;并且发生在发育中的、衰老的、健康的或患病的大脑中。因此,令人印象深刻的细胞可塑性水平似乎是小胶质细胞多效性生物学功能的必要条件。表观遗传变化,包括组蛋白修饰或DNA甲基化以及微小RNA表达,是基因表达的重要调节因子,并参与细胞表型调节和重编程,因此是调节细胞可塑性机制的一部分。在这里,我们回顾并讨论表观遗传机制,这些机制正在成为这种小胶质细胞可塑性的促成因素,因此可能构成调节与小胶质细胞相关的脑部疾病(包括发育性疾病、神经退行性疾病以及癌症)的有趣靶点。