Paraventricular nucleus CRH neurons regulate acute lung injury via sympathetic nerve–neutrophil axis

Hui Li (), Tao Liu, Yang Wang, Xue-Mei Miao, Yi-Yu Xiong, Qian Zhao, Wei-Yun Shen, Fu-Hong Su, Kang Chen and Ru-Ping Dai ()
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Hui Li: Central South University
Tao Liu: Central South University
Yang Wang: Central South University
Xue-Mei Miao: Central South University
Yi-Yu Xiong: Central South University
Qian Zhao: Central South University
Wei-Yun Shen: Central South University
Fu-Hong Su: Erasmus Hospital
Kang Chen: Wayne State University
Ru-Ping Dai: Central South University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe conditions with high morbidity and mortality with limited effective therapies. Neuroimmune interactions play a critical role in lung homeostasis, but it remains unclear if specific brain regions regulate lung inflammation. Here, we perform anatomical tracing, chemogenetic modulation, and pharmacological interventions in male mice and identify a neural circuit from corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (CRHPVN neurons) to the lung. The activation of these neurons protects mice from ALI and promotes survival, reduces neutrophil infiltration and effector functions in the lung, whereas inhibiting CRHPVN neurons worsens ALI. The protective effect is mediated by increased sympathetic nervous activity, with locally released norepinephrine modulating neutrophil functions via β2-AR–β-arrestin2 signaling to inhibit the NF-κB pathway. These findings uncover a brain-lung neural circuit that modulates immune responses during ALI, offering a potential therapeutic target for ALI and ARDS.

Date: 2025
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DOI: 10.1038/s41467-025-63953-7

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