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机械力刺激通过 PIEZO1 感知对于先天免疫至关重要。

Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity.

机构信息

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.

Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

出版信息

Nature. 2019 Sep;573(7772):69-74. doi: 10.1038/s41586-019-1485-8. Epub 2019 Aug 21.

DOI:10.1038/s41586-019-1485-8
PMID:31435009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6939392/
Abstract

Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response. Here we show that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiates an inflammatory response via the mechanically activated ion channel PIEZO1. Mice lacking PIEZO1 in innate immune cells showed ablated pulmonary inflammation in the context of bacterial infection or fibrotic autoinflammation. Our results reveal an environmental sensory axis that stimulates innate immune cells to mount an inflammatory response, and demonstrate a physiological role for PIEZO1 and mechanosensation in immunity.

摘要

先天免疫细胞直接识别入侵病原体是炎症反应的关键驱动因素。然而，先天免疫系统的细胞也可以感知其局部微环境，并对温度、pH 值、氧气和营养物质可用性的生理波动做出反应，而这些波动在炎症期间会发生改变。尽管免疫系统的细胞在其生命周期中会受到力和压力的作用，但人们对这些机械过程如何调节免疫反应知之甚少。在这里，我们表明，类似于免疫细胞在肺部经历的周期性流体静压力通过机械激活离子通道 PIEZO1 引发炎症反应。在细菌感染或纤维性自身炎症的情况下，先天免疫细胞中缺乏 PIEZO1 的小鼠表现出肺部炎症的缺失。我们的结果揭示了一个环境感应轴，该轴刺激先天免疫细胞引发炎症反应，并证明了 PIEZO1 和机械感觉在免疫中的生理作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa73/6939392/6de1b5644f9e/nihms-1061326-f0003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa73/6939392/ed1290565ed9/nihms-1061326-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa73/6939392/ad784928f1b2/nihms-1061326-f0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa73/6939392/25e48be7d5f5/nihms-1061326-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa73/6939392/54c137869dea/nihms-1061326-f0010.jpg
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