Local sympathetic innervations modulate the lung innate immune responses
Local sympathetic innervations modulate the lung innate immune responses
复制标题
局部交感神经支配调节肺部先天免疫反应
DOI：
10.1126/sciadv.aay1497
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发表时间：
2020-05-01
期刊：
影响因子：
13.6
通讯作者：
Yang, Jing
中科院分区：
文献类型：
--
作者：
Liu, Tingting;Yang, Lu;Yang, Jing
肺部的局部免疫力需要受到严格控制。然而，传出神经信号如何影响肺部免疫仍不完全清楚。在这里，我们报告了基于 iDISCO 的改进协议 iDISCO(ace) 的开发，用于对完整、未切片肺组织中的神经神经支配和免疫反应进行全组织 3D 评估。我们观察到，遗传、药理学或手术切除局部交感神经支配可促进 LPS 引发肺部先天免疫反应。此外，交感神经消融增强了 IL-33 引发的 2 型先天免疫。我们进一步表明，交感神经递质去甲肾上腺素或β2-肾上腺素能受体的特异性激动剂可以以细胞内在的方式抑制LPS或IL-33引发的免疫反应。此外，β2-肾上腺素能受体的基因缺失产生了与交感神经消融所观察到的免疫调节作用类似的免疫调节作用。总之，这项研究阐明了局部交感神经支配在负向调节肺部先天免疫反应中的关键功能。
Local immunity of the lung needs to be under tight control. However, how efferent neural signals influence lung immunity remains incompletely understood. Here, we report the development of a modified iDISCO-based protocol, iDISCO(ace), for whole-tissue 3D assessment of neural innervations and immune reactions in intact, unsectioned lung tissues. We observed that genetic, pharmacologic, or surgical removal of local sympathetic innervations promoted LPS-elicited innate immune response in the lung. Also, sympathetic ablation enhanced IL-33-elicited type 2 innate immunity. We further show that the sympathetic neurotransmitter norepinephrine, or specific agonists of the beta 2-adrenergic receptor, can inhibit the LPS- or IL-33-elicited immune response in a cell-intrinsic manner. Moreover, genetic deletion of the beta 2-adrenergic receptor produced immunomodulatory effects similar to those observed with sympathetic ablation. Together, this study elucidates the critical function of local sympathetic innervations in negatively modulating the lung innate immune responses.