Eosinophils regulate intra-adipose axonal plasticity.
Eosinophils regulate intra-adipose axonal plasticity.
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嗜酸性粒细胞调节脂肪内轴突可塑性
DOI：
10.1073/pnas.2112281119
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发表时间：
2022-01-18
影响因子：
11.1
通讯作者：
Zeng W
中科院分区：
文献类型：
--
作者：
Meng X;Qian X;Ding X;Wang W;Yin X;Zhuang G;Zeng W
脂肪组织中的神经支配在调节脂肪产热能力和代谢稳态中起着至关重要的作用。在改变神经元对代谢状态的控制的生理和病理条件下，组织范围的神经显示出很大程度的结构可塑性。我们在这里发现，神经元的可塑性是由免疫细胞调节的，这构成了一种有吸引力的方式来重塑神经控制的能量平衡，通过靶向免疫成分。交感神经支配调节能量平衡，脂肪组织中的神经密度在各种代谢状态下发生变化，导致神经元控制改变并赋予对代谢挑战的弹性。然而，免疫环境对神经元神经支配的影响尚不清楚。在这里，我们研究了嗜酸性粒细胞对神经可塑性的调节作用，发现它们在白色脂肪组织（WAT）中增加了细胞丰度，并产生神经生长因子（NGF）。嗜酸性粒细胞中Ngf的缺失或嗜酸性粒细胞的耗竭损害冷诱导的轴突生长和beiging过程。交感神经、表达IL-33的基质细胞和嗜酸性粒细胞之间的空间接近在人和小鼠脂肪组织中均可见。在细胞水平上，交感肾上腺素能信号诱导基质细胞中的钙流和随后的IL-33释放，这驱动了来自第2组先天淋巴样细胞（ILC 2）的IL-5的上调，导致嗜酸性粒细胞的增加。我们提出了交感神经活动和2型免疫之间的前馈回路，协调增强交感神经支配，促进能量消耗。
Significance Neuronal innervation in the adipose tissues plays a crucial role in regulating adipose thermogenic capacity and metabolic homeostasis. The tissue-wide nerves display a large extent of structural plasticity under physiological and pathological conditions that alter the neuronal control of metabolic states. We find here that neuronal plasticity is regulated by immune cells, which constitutes an appealing way to reshape neural-controlled energy balance by targeting immune components. Sympathetic innervation regulates energy balance, and the nerve density in the adipose tissues changes under various metabolic states, resulting in altered neuronal control and conferring resilience to metabolic challenges. However, the impact of the immune milieu on neuronal innervation is not known. Here, we examined the regulatory role on nerve plasticity by eosinophils and found they increased cell abundance in response to cold and produced nerve growth factor (NGF) in the white adipose tissues (WAT). Deletion of Ngf from eosinophils or depletion of eosinophils impairs cold-induced axonal outgrowth and beiging process. The spatial proximity between sympathetic nerves, IL-33–expressing stromal cells, and eosinophils was visualized in both human and mouse adipose tissues. At the cellular level, the sympathetic adrenergic signal induced calcium flux in the stromal cells and subsequent release of IL-33, which drove the up-regulation of IL-5 from group 2 innate lymphoid cells (ILC2s), leading to eosinophil accretion. We propose a feed-forward loop between sympathetic activity and type 2 immunity that coordinately enhances sympathetic innervation and promotes energy expenditure.
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影响因子：
7.7
作者：
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通讯作者：
Elmquist JK
影响因子：
17.1
作者：
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影响因子：
21.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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