Section of Histology anf Human Anatomy, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy.
Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Viale Gaetano Pieraccini, 50139 Florence, Italy.
Cells. 2021 May 13;10(5):1195. doi: 10.3390/cells10051195.
Different cell populations in the nervous tissue establish numerous, heterotypic interactions and perform specific, frequently intersecting activities devoted to the maintenance of homeostasis. Microglia and astrocytes, respectively the immune and the "housekeeper" cells of nervous tissue, play a key role in neurodegenerative diseases. Alterations of tissue homeostasis trigger neuroinflammation, a collective dynamic response of glial cells. Reactive astrocytes and microglia express various functional phenotypes, ranging from anti-inflammatory to pro-inflammatory. Chronic neuroinflammation is characterized by a gradual shift of astroglial and microglial phenotypes from anti-inflammatory to pro-inflammatory, switching their activities from cytoprotective to cytotoxic. In this scenario, the different cell populations reciprocally modulate their phenotypes through intense, reverberating signaling. Current evidence suggests that heterotypic interactions are links in an intricate network of mutual influences and interdependencies connecting all cell types in the nervous system. In this view, activation, modulation, as well as outcomes of neuroinflammation, should be ascribed to the nervous tissue as a whole. While the need remains of identifying further links in this network, a step back to rethink our view of neuroinflammation in the light of the "whole system" scale, could help us to understand some of its most controversial and puzzling features.
神经组织中的不同细胞群体建立了众多异质相互作用，并执行特定的、经常重叠的活动，以维持体内平衡。小胶质细胞和星形胶质细胞分别是神经组织的免疫细胞和“管家细胞”，在神经退行性疾病中发挥着关键作用。组织内稳态的改变会引发神经炎症，这是一种胶质细胞的集体动态反应。反应性星形胶质细胞和小胶质细胞表达各种功能表型，从抗炎到促炎。慢性神经炎症的特征是星形胶质细胞和小胶质细胞表型从抗炎向促炎逐渐转变，使它们的活性从细胞保护转变为细胞毒性。在这种情况下，不同的细胞群体通过强烈的、回荡的信号相互调节它们的表型。目前的证据表明，异质相互作用是连接神经系统中所有细胞类型的复杂相互影响和相互依存网络中的纽带。从这个角度来看，神经炎症的激活、调节以及后果都应该归因于整个神经组织。虽然在这个网络中还需要进一步确定其他联系，但退后一步，从“整体系统”的角度重新思考我们对神经炎症的看法，可能有助于我们理解其一些最具争议和令人困惑的特征。
