A vagal-to-sympathetic reflex controls lung vascular leak

Activating CYSLTR2-expressing vagal afferent neurons rapidly increases lung vascular leak within minutes, causing perivascular edema and respiratory dysfunction in the lung.

• Why it matters: Sustained lung vascular leak is costly during inflammation, but upstream neural regulators of the vascular barrier remain largely unidentified.
• What they did: A chemogenetic screen of vagal afferent subtypes identified an orphan Cysltr2 neuron population innervating alveolar capillary beds; activating or silencing these neurons during inhaled allergen challenge tested leak and lung mechanics.
• The result: Silencing CYSLTR2 neurons during inhaled allergen challenge reduces leak and improves lung mechanics, indicating a vagal-to-brainstem-to-sympathetic reflex that regulates fluid balance upstream of endothelium.