Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function.
Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function.
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DOI：
10.3389/fimmu.2021.703527
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发表时间：
2021
影响因子：
7.3
通讯作者：
Cheadle L
中科院分区：
文献类型：
--
作者：
Ferro A;Auguste YSS;Cheadle L
细胞间信号分子，如细胞因子及其受体，使免疫细胞能够相互通信，并与周围的微环境进行通信。新出现的证据表明，在大脑外调节损伤和疾病的炎症反应的相同信号通路，在大脑发育、可塑性和功能方面也发挥着强大的作用。这些观察结果提出了这样一个问题：与中枢神经系统相比，同样的信号分子如何在外周组织中发挥如此不同的作用？此前，中枢神经系统被认为在很大程度上免受炎症信号的影响。在这里，我们回顾了细胞因子等免疫信号分子在大脑中的特殊作用在很大程度上是由神经活动塑造的证据，神经活动是大脑的一个关键特征，反映了突触神经元之间的活跃交流。我们讨论了已知的机制，通过参与经典的炎症信号级联来组装、重塑和消除突触，小胶质细胞是大脑的常驻免疫细胞，通过参与活动的增加和减少来响应活动的增加和减少。我们整合了来自(1)小胶质细胞-神经元相互作用的活体成像研究，(2)跨多个神经回路的发育研究，以及(3)小胶质细胞和神经元中活性依赖基因表达的分子研究，以强调活动在定义大脑中免疫途径功能方面的特定作用。鉴于跨不同组织的信号通路的重新用途可能是克服基因组大小有限的重要进化策略，了解细胞因子功能是如何在大脑中建立和维持的，可能会导致对神经健康和疾病的关键洞察。
Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.
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影响因子：
16.2
作者：
Cheadle L;Rivera SA;Phelps JS;Ennis KA;Stevens B;Burkly LC;Lee WA;Greenberg ME
通讯作者：
Greenberg ME
影响因子：
2.4
作者：
Akbar, Umar;Ashizawa, Tetsuo
通讯作者：
Ashizawa, Tetsuo
影响因子：
--
作者：
Fujita Y;Yamashita T
通讯作者：
Yamashita T
影响因子：
56.9
作者：
Beattie, EC;Stellwagen, D;Malenka, RC
通讯作者：
Malenka, RC
影响因子：
3.3
作者：
Bertot, Charlotte;Groc, Laurent;Avignone, Elena
通讯作者：
Avignone, Elena