Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation

Sébastien Talbot, Raja Elie E. Abdulnour, Patrick R. Burkett, Seungkyu Lee, Shane J.F. Cronin, Maud A. Pascal, Cedric Laedermann, Simmie L. Foster, Johnathan V. Tran, Nicole Lai, Isaac M. Chiu, Nader Ghasemlou, Matthew DiBiase, David Roberson, Christian Von Hehn, Busranour Agac, Oliver Haworth, Hiroyuki Seki, Josef M. Penninger, Vijay K. KuchrooBruce P. Bean, Bruce D. Levy, Clifford J. Woolf

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119 Citations (Scopus)

Abstract

Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. Incontrast, ablating Nav1.8+ sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced byactivated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4+ and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. Talbot etal. provide mechanistic insights into how neuro-immune interplay amplifies type 2 allergic airway inflammation. Based on this, they propose a new treatment strategy for asthma, using charged sodium channel blockers to selectively silence sensory neurons in the lung.

Original languageEnglish
Pages (from-to)341-354
Number of pages14
JournalNeuron
Volume87
Issue number2
DOIs
Publication statusPublished - 2015 Jul 15

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Talbot, S., Abdulnour, R. E. E., Burkett, P. R., Lee, S., Cronin, S. J. F., Pascal, M. A., Laedermann, C., Foster, S. L., Tran, J. V., Lai, N., Chiu, I. M., Ghasemlou, N., DiBiase, M., Roberson, D., Von Hehn, C., Agac, B., Haworth, O., Seki, H., Penninger, J. M., ... Woolf, C. J. (2015). Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation. Neuron, 87(2), 341-354. https://doi.org/10.1016/j.neuron.2015.06.007