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

研究成果: Article査読

209 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)341-354
ページ数14
ジャーナルNeuron
87
2
DOI
出版ステータスPublished - 2015 7月 15

ASJC Scopus subject areas

  • 神経科学(全般)

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