Postprandial parasympathetic signals promote lung type 2 immunity

Area of Science:

• Neuroimmunology
• Pulmonology
• Gastroenterology

Background:

• Lung type 2 immunity is crucial for host defense but its dysregulation contributes to asthma.
• Asthma symptoms can worsen after eating, a postprandial phenomenon with unclear mechanisms.

Purpose of the Study:

• To investigate the link between feeding, parasympathetic activation, and lung type 2 immunity.
• To elucidate the neuroimmune mechanisms underlying postprandial exacerbation of lung inflammation.

Main Methods:

• Studied lung type 2 immunity and parasympathetic activity in mice after feeding.
• Utilized pharmacological and chemogenetic approaches to modulate parasympathetic signals.
• Investigated the role of the cholinergic receptor muscarinic 4 (Chrm4) in lung group 2 innate lymphoid cells (ILC2s).

Main Results:

• Feeding enhanced lung type 2 immunity, correlating with parasympathetic activation.
• Parasympathetic signals spatially engaged with ILC2-mediated immune responses.
• Blocking parasympathetic signals reduced lung type 2 immunity; manipulating these signals modulated immune responses.
• Chrm4 deletion in ILC2s mitigated lung inflammation in mice and humans.

Conclusions:

• The parasympathetic nervous system plays a critical role in modulating lung type 2 immunity post-feeding.
• A gut-brain-lung reflex involving acetylcholine and Chrm4 on ILC2s contributes to lung inflammation.
• These findings reveal a novel neuroimmune axis relevant to asthma pathophysiology.