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

Summary

Using anatomical tracing, chemogenetics, and pharmacology in male mice, the authors identify a brain–lung circuit whereby PVN CRH neurons regulate acute lung injury via a sympathetic nerve–neutrophil axis. Manipulating this circuit modulated lung inflammation, highlighting neuroimmune control as a targetable mechanism in ALI/ARDS.

Key Findings

• Identified a PVN CRH neuron–driven neural circuit that regulates lung inflammation via a sympathetic nerve–neutrophil axis in mice.
• Chemogenetic modulation of PVN CRH neurons altered the severity of acute lung injury.
• Pharmacological interventions affecting the circuit components modulated pulmonary inflammatory responses.

Clinical Implications

While preclinical, the findings support exploration of neuromodulatory strategies (e.g., targeting hypothalamic or sympathetic pathways) to mitigate inflammation in ALI/ARDS.

Limitations

• Findings are limited to male mice; sex differences and human relevance remain to be established
• Translational gap and potential off-target effects of chemogenetic/pharmacologic tools

Future Directions

Validate the circuit in female and large-animal models, define efferent autonomic pathways, and assess feasibility of clinical neuromodulation to reduce lung inflammation.