Details

Autor(en) / Beteiligte

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

Titel

Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation

Ist Teil von

• Neuron (Cambridge, Mass.), 2015-07, Vol.87 (2), p.341-354

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. •Nociceptor sensory neuron ablation reduces allergic airway inflammation•QX-314 enters through large-pore ion channels to silence airway sensory neurons•IL-5 triggers sensory neuron release of peptides that drive immune cell responses•Silencing nociceptors is a new strategy to treat type 2 inflammation and allergies Talbot et al. 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.