DataVXAdvanced SciencePaper
journal article·2026-02Open access

Neural Circuits between Nodose Ganglion and Pulmonary Neuroendocrine Cells Regulate Lung Inflammatory Responses

Jie Chen, Shitao Xie, Zhekai Lin, Caiqi Zhao, Rujia Tao, Yingying Ma, Xiaoyan Chen, Renlan Wu, Qingjian Han, Pengfei Sui, Sheng Wang, Hongbin Ji, Hai Song, Xiaoming Zhang, Yangang Sun, Yuanlin Song, Xiao Su

Advanced Science· Volume 13· Issue 12
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Source abstract

Abstract

ABSTRACT The lungs interface directly with the external environment, exposing them to airborne pathogens like endotoxins. We investigated whether the vagus nerve, which innervates the lungs‐detects such pathogens. Using transcriptomics, tissue clearance imaging, electrophysiology, and cell‐specific knockout models, we discovered that vagal sensory endings synapse with pulmonary neuroendocrine cells (PNECs). These nerve endings detect bacterial endotoxins primarily through the pain receptor TRPA1, not via Toll‐like receptor 4 (TLR4). This detection triggers electrical excitation in vagal neurons and upregulates neuropeptide (e.g., αCGRP) production in the nodose ganglia. Released αCGRP then acts back on PNECs, stimulating their neuropeptide synthesis and proliferation. This creates a feed‐forward loop that amplifies endotoxin‐induced lung inflammation. Our findings reveal a critical neural circuit between the nodose ganglion and PNECs that regulates pulmonary inflammatory responses.
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Research context

OpenAlex topics: Vagus Nerve Stimulation Research · Respiratory and Cough-Related Research · Neuroscience of respiration and sleep

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Shanghai Institute of Materia Medica Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai China

Shanghai Key Laboratory of Lung Inflammation and Injury Department of Pulmonary Medicine Zhongshan Hospital Fudan University Shanghai China

Institutes of Brain Science Fudan University Shanghai China

Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences Shanghai China

Department of Neurobiology Hebei Medical University Hebei China

The MOE Key Laboratory of Biosystems Homeostasis and Protection Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University Hangzhou Zhejiang China

Institute of Neuroscience State Key Laboratory of Neuroscience Center for Excellence in Brain Science & Intelligence Technology Chinese Academy of Sciences Shanghai China

Funding

National Natural Science Foundation of China · Science and Technology Commission of Shanghai Municipality · China Postdoctoral Science Foundation · Key Technologies Research and Development Program

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