Chemokines are important signaling molecules in the immune and nervous system. Using a fluorescence reporter mouse model, we demonstrate that the chemokine CCL17, a ligand of the chemokine receptor CCR4, is produced in the murine brain, particularly in a subset of hippocampal CA1 neurons. We found that basal expression of Ccl17 in hippocampal neurons was strongly enhanced by peripheral challenge with lipopolysaccharide (LPS). LPS‐mediated induction of Ccl17 in the hippocampus was dependent on local tumor necrosis factor (TNF) signaling, whereas upregulation of Ccl22 required granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). CCL17 deficiency resulted in a diminished microglia density under homeostatic and inflammatory conditions. Further, microglia from naïve Ccl17‐deficient mice possessed a reduced cellular volume and a more polarized process tree as assessed by computer‐assisted imaging analysis. Regarding the overall branching, cell surface area, and total tree length, the morphology of microglia from naïve Ccl17‐deficient mice resembled that of microglia from wild‐type mice after LPS stimulation. In line, electrophysiological recordings indicated that CCL17 downmodulates basal synaptic transmission at CA3–CA1 Schaffer collaterals in acute slices from naïve but not LPS‐treated animals. Taken together, our data identify CCL17 as a homeostatic and inducible neuromodulatory chemokine affecting the presence and morphology of microglia and synaptic transmission in the hippocampus.

中文翻译：

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CCL17发挥神经免疫调节功能，并在海马神经元中表达

趋化因子是免疫和神经系统中重要的信号分子。使用荧光记者小鼠模型，我们证明了趋化因子CCL17，趋化因子受体CCR4的配体，是在鼠脑中产生的，尤其是在海马CA1神经元的一个子集中。我们发现，脂多糖（LPS）的外周攻击极大地增强了海马神经元中Ccl17的基础表达。LPS介导的海马Ccl17的诱导依赖于局部肿瘤坏死因子（TNF）信号传导，而Ccl22的上调所需的粒细胞-巨噬细胞集落刺激因子（GM-CSF）。CCL17缺乏导致在稳态和炎症条件下小胶质细胞密度降低。此外，通过计算机辅助成像分析评估，来自幼稚的Ccl17缺陷小鼠的小胶质细胞具有减少的细胞体积和极化的过程树。关于整体分支，细胞表面积和总树长，来自幼稚Ccl17的小胶质细胞的形态LPS刺激后，缺陷小鼠类似于野生型小鼠的小胶质细胞。符合条件的是，电生理记录表明，CCL17下调了来自天真但未经LPS处理的动物的急性切片中CA3–CA1 Schaffer侧支的基础突触传递。两者合计，我们的数据确定CCL17是一种稳定和可诱导的神经调节趋化因子，影响小胶质细胞的存在和形态以及海马中的突触传递。