Department of Neuroscience, Center for Brain Immunology and Glia (BIG), Charlottesville, VA, USA.
Neuroscience Graduate Program, Charlottesville, VA, USA.
Nat Rev Immunol. 2021 Jul;21(7):454-468. doi: 10.1038/s41577-020-00487-7. Epub 2021 Jan 21.
The immune and nervous systems have unique developmental trajectories that individually build intricate networks of cells with highly specialized functions. These two systems have extensive mechanistic overlap and frequently coordinate to accomplish the proper growth and maturation of an organism. Brain resident innate immune cells - microglia - have the capacity to sculpt neural circuitry and coordinate copious and diverse neurodevelopmental processes. Moreover, many immune cells and immune-related signalling molecules are found in the developing nervous system and contribute to healthy neurodevelopment. In particular, many components of the innate immune system, including Toll-like receptors, cytokines, inflammasomes and phagocytic signals, are critical contributors to healthy brain development. Accordingly, dysfunction in innate immune signalling pathways has been functionally linked to many neurodevelopmental disorders, including autism and schizophrenia. This review discusses the essential roles of microglia and innate immune signalling in the assembly and maintenance of a properly functioning nervous system.
免疫系统和神经系统具有独特的发育轨迹，各自构建具有高度专业化功能的复杂细胞网络。这两个系统具有广泛的机制重叠，并经常协调以完成生物体的适当生长和成熟。大脑驻留的先天免疫细胞——小胶质细胞——具有塑造神经回路和协调大量不同神经发育过程的能力。此外，许多免疫细胞和与免疫相关的信号分子存在于发育中的神经系统中，并有助于健康的神经发育。特别是，先天免疫系统的许多成分，包括 Toll 样受体、细胞因子、炎性小体和吞噬信号，都是健康大脑发育的重要贡献者。因此，先天免疫信号通路的功能障碍与许多神经发育障碍有关，包括自闭症和精神分裂症。这篇综述讨论了小胶质细胞和先天免疫信号在正常运作的神经系统的组装和维持中的重要作用。
