Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation

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

TitleSilencing Nociceptor Neurons Reduces Allergic Airway Inflammation
TypeJournal article
AuthorsTalbot, S.
Abdulnour, R.
Burkett, P.
Lee, S.
Cronin, S.
Pascal, M.
Laedermann, C.
Foster, S.
Tran, J.
Lai, N.
Chiu, I.
Ghasemlou, N.
DiBiase, M.
Roberson, D.
Von Hehn, C.
Agac, B.
Haworth, O.
Seki, H.
Penninger, J.
Kuchroo, V.
Bean, B.
Levy, B.
Woolf, C.
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. In contrast, 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 by activated 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.

Keywordsinflammation, Nociceptor Neurons, asthma, lung
JournalNeuron
Journal citation87 (2), pp. 341-354
ISSN0896-6273
Year2015
PublisherCell Press
Publisher's version
Digital Object Identifier (DOI)https://doi.org/10.1016/j.neuron.2015.06.007
Publication dates
Published25 Jun 2015

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