Data from: Nociceptor neurons control pollution-mediated neutrophilic asthma

The immune and sensory nervous systems, having evolved in parallel,
communicate through shared receptors and transmitters to maintain
homeostasis and respond to both external and internal disruptions.
Although neural responses often confer protective benefits, they can also
exacerbate inflammation during allergic reactions such as asthma. In our
study, we modeled pollution-exacerbated asthma by exposing mice to ambient
PM2.5 particles alongside ovalbumin. Compared to exposure to ovalbumin
alone, this co-exposure significantly increased the numbers of neutrophils
and γδ T cells in bronchoalveolar lavage fluid and lung tissue,
respectively. We found that silencing nociceptor neurons at the peak of
inflammation using intranasal QX-314 or ablating Trpv1-expressing neurons
reduced lung neutrophil accumulation. Live in vivo intravital imaging
confirmed that neuronal ablation reduced neutrophil numbers and increased
their net displacement capacity. In neurons isolated from mice with
pollution-exacerbated asthma, the chemical-sensing TRPA1 channel exhibited
heightened sensitivity to its cognate ligand. Elevated levels of artemin
were detected in the bronchoalveolar lavage fluid of pollution-exposed
mice but returned to baseline in mice with ablated nociceptor neurons.
Alveolar macrophages expressing the pollution-sensing aryl hydrocarbon
receptor were identified as a putative source of artemin following
exposure to PM2.5. This molecule enhanced TRPA1 responsiveness and, in
turn, drove nociceptor-mediated neutrophil recruitment, revealing a novel
mechanism by which lung-innervating neurons respond to air pollution in
the context of allergy. Overall, our findings suggest that targeting
artemin-driven pathways could provide a therapeutic strategy for
controlling neutrophilic airway inflammation in asthma, a clinical
condition typically refractory to treatment.