NEBS AND PIEZO2: GUARDIANS OF THE RESPIRATORY GALAXY

In a recent Nature publication, Schappe, M (2024) & team at Harvard Medical School uncover a fascinating role of sensory neurons in guarding against airway obstruction and orchestrating crucial reflexes to maintain respiratory function.

How Neuroepithelial Bodies Detect Airway Closure and Regulate Respiratory Reflexes

How does the respiratory system detect airway closure and respond before it becomes dangerous? A recent Nature study by Schappe et al. (2024) identified a specialized sensory pathway involving neuroepithelial bodies (NEBs), the mechanosensitive ion channel PIEZO2, and vagal sensory neurons.

The findings reveal an important mechanism for airway mechanosensation, showing how NEBs detect mechanical changes in the airway and contribute to protective respiratory reflexes such as gasping.

Key Findings

NEBs act as airway sensors
The researchers identified NEBs as important sites of airway mechanosensation. Their activation stimulates vagal sensory pathways involved in respiratory reflexes.

PIEZO2 detects mechanical changes
PIEZO2 plays a critical role in sensing airway closure. Deletion of PIEZO2 specifically in NEBs abolished airway-closure-induced gasping, highlighting its importance in this pathway.

NEBs are essential for gasping responses
NEBABLATE mice did not gasp following airway closure, suction, or methacholine exposure. They also showed reduced compensatory changes in tidal volume during airway compression and reduced spontaneous sigh frequency.

NEBs influence lung mechanics
Mice lacking NEB-associated PIEZO2 showed reduced inspiratory capacity and lung compliance, demonstrating a connection between NEB signaling and respiratory mechanics.

Measuring Respiratory Function

The study combined molecular and neural approaches with preclinical respiratory physiology measurements. Thoracic compression produced measurable changes in lung mechanics, including decreased lung compliance, assessed using the flexiVent.

vivoFlow plethysmography was also used to characterize respiratory responses following chemogenetic activation of NEBs, providing complementary measurements of breathing patterns and respiratory function.

A New Perspective on Airway Mechanosensation

Together, the findings support a NEB–PIEZO2–vagal sensory pathway:

Airway closure → NEB activation → PIEZO2 sensing → vagal signaling → respiratory reflex

This pathway provides new insight into how the respiratory system detects airway obstruction and rapidly adjusts breathing.

Understanding these mechanisms could help advance research into respiratory conditions involving airway obstruction, altered lung mechanics, and abnormal respiratory reflexes, while also raising interesting questions about the biological mechanisms underlying sensations such as air hunger.

Key Takeaways

• NEBs are important sensors of airway closure.
• PIEZO2 enables NEBs to detect mechanical changes.
• NEBs activate vagal sensory pathways that contribute to gasping.
• Loss of NEBs or PIEZO2 alters respiratory responses and lung mechanics.
• flexiVent and vivoFlow plethysmography provide complementary tools for characterizing pulmonary mechanics and respiratory function in preclinical models.