Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Nat Neurosci. 2018 Jun;21(6):779-786. doi: 10.1038/s41593-018-0145-x. Epub 2018 May 7.
Microglia differentiate from progenitors that infiltrate the nascent CNS during early embryonic development. They then remain in this unique immune-privileged environment throughout life. Multiple immune mechanisms, which we collectively refer to as microglial checkpoints, ensure efficient and tightly regulated microglial responses to perturbations in the CNS milieu. Such mechanisms are essential for proper CNS development and optimal physiological function. However, in chronic disease or aging, when a robust immune response is required, such checkpoint mechanisms may limit the ability of microglia to protect the CNS. Here we survey microglial checkpoint mechanisms and their roles in controlling microglial function throughout life and in disease, and discuss how they may be targeted therapeutically.
小胶质细胞由胚胎早期浸润新生中枢神经系统的前体细胞分化而来。此后，它们在整个生命周期中都处于这种独特的免疫特权环境中。我们统称多种免疫机制为小胶质细胞检查点，以确保小胶质细胞对中枢神经系统微环境变化的有效和严格调控反应。这些机制对于中枢神经系统的正常发育和最佳生理功能至关重要。然而，在慢性疾病或衰老时，当需要强烈的免疫反应时，这种检查点机制可能会限制小胶质细胞保护中枢神经系统的能力。在这里，我们调查了小胶质细胞检查点机制及其在控制整个生命周期和疾病中小胶质细胞功能中的作用，并讨论了如何对其进行治疗性靶向。
