MrgprC11⁺ Jugular Neurons Control Airway Hyperresponsiveness in Allergic Airway Inflammation

Area of Science:

• Neuroscience
• Pulmonology
• Immunology

Background:

• The lung is innervated by vagal sensory neurons, originating from nodose and jugular ganglia.
• Jugular ganglia neurons' role in lung function, particularly in asthma, is poorly understood.
• MrgprC11-positive jugular neurons were previously shown to mediate cholinergic bronchoconstriction.

Purpose of the Study:

• To investigate the role of MrgprC11-positive jugular sensory neurons in a mouse model of allergic asthma.
• To identify other Mrgpr family members expressed in jugular neurons.
• To explore the influence of cytokines IL-4 and oncostatin M on jugular neuron function.

Main Methods:

• Utilized a mouse allergic asthma model.
• Investigated expression of Mrgpr family members, IL-4, and oncostatin M receptors in jugular neurons.
• Examined the effect of IL-4 and oncostatin M on MrgprC11-positive jugular neuron responses.
• Assessed airway hyperresponsiveness after ablation of MrgprC11-positive neurons.

Main Results:

• Identified MrgprA3, MrgprB4, and MrgprD as co-expressed with MrgprC11 in jugular sensory neurons.
• Demonstrated dense innervation of the respiratory tract by MrgprC11-positive jugular neurons.
• Showed that IL-4 and oncostatin M sensitize MrgprC11-positive jugular neurons.
• Found that ablation of MrgprC11-positive neurons significantly reduced airway hyperresponsiveness in asthmatic mice.

Conclusions:

• Jugular sensory neurons, particularly MrgprC11-positive ones, are critical in mediating airway constriction in allergic asthma.
• These neurons represent a potential therapeutic target for managing airway hyperresponsiveness.
• Further research into jugular sensory neuron function is warranted for respiratory disease treatment.