Microglial identity and inflammatory responses are controlled by the combined effects of neurons and astrocytes.
Microglial identity and inflammatory responses are controlled by the combined effects of neurons and astrocytes.
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小胶质细胞的特性和炎症反应由神经元和星形胶质细胞的共同作用控制。
DOI：
10.1016/j.celrep.2021.108882
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发表时间：
2021-03-23
期刊：
影响因子：
8.8
通讯作者：
Qiu J
中科院分区：
文献类型：
--
作者：
Baxter PS;Dando O;Emelianova K;He X;McKay S;Hardingham GE;Qiu J
小胶质细胞，脑内驻留的巨噬细胞，需要来自CNS微环境的指令来维持其身份和形态并调节炎症反应，尽管介导这一过程的机制尚不清楚。在这里，我们表明，神经元和星形胶质细胞合作，以促进小胶质细胞分支，诱导表达的小胶质细胞的签名基因通常失去了在体外和在年龄和疾病在体内，并抑制感染和损伤相关的基因集。神经元和星形胶质细胞分别对小胶质细胞的影响很弱，表明这些细胞类型之间的协同作用，其通过涉及转化生长因子β2（TGF-β2）信号传导的机制发挥作用。神经元和星形胶质细胞也联合收割机提供免疫调节线索，抑制对弱炎症刺激的引发的小胶质细胞反应（不影响最大反应），从而限制炎症对神经元和星形胶质细胞本身的反馈作用。这些发现解释了为什么离体分离的小胶质细胞经历去分化和炎症失调，并指出如何抵消疾病和年龄相关的变化。神经元和星形胶质细胞结合联合收割机以促进小胶质细胞的自我平衡特征这挽救了在离体小胶质细胞和疾病中发生的变化从机制上讲，这涉及转化生长因子β 2（TBGF-β2）信号传导神经元和星形胶质细胞也抑制小胶质细胞的炎症反应巴克斯特等人。表明小胶质细胞从健康状态到疾病相关状态的转化可以通过涉及TBGF-β2信号传导的机制被神经元和星形胶质细胞的联合作用抑制。它们还抑制小胶质细胞对温和刺激的过度反应，并限制来自激活的小胶质细胞的反馈信号。
Microglia, brain-resident macrophages, require instruction from the CNS microenvironment to maintain their identity and morphology and regulate inflammatory responses, although what mediates this is unclear. Here, we show that neurons and astrocytes cooperate to promote microglial ramification, induce expression of microglial signature genes ordinarily lost in vitro and in age and disease in vivo, and repress infection- and injury-associated gene sets. The influence of neurons and astrocytes separately on microglia is weak, indicative of synergies between these cell types, which exert their effects via a mechanism involving transforming growth factor β2 (TGF-β2) signaling. Neurons and astrocytes also combine to provide immunomodulatory cues, repressing primed microglial responses to weak inflammatory stimuli (without affecting maximal responses) and consequently limiting the feedback effects of inflammation on the neurons and astrocytes themselves. These findings explain why microglia isolated ex vivo undergo de-differentiation and inflammatory deregulation and point to how disease- and age-associated changes may be counteracted. Neurons and astrocytes combine to promote the microglial homeostatic signature This rescues changes that happen in microglia ex vivo and in disease Mechanistically, this involves transforming growth factor beta 2 (TBGF-β2) signaling Neurons and astrocytes also repress microglial inflammatory responses Baxter et al. show that the transformation of microglia from a healthy to disease-associated state can be suppressed by the combined actions of neurons and astrocytes via a mechanism involving TBGF-β2 signaling. They also repress exaggerated microglial responses to mild stimuli and limit the feedback signaling from activated microglia.
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