Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.
Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.
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DOI：
10.1016/j.neuron.2015.06.007
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发表时间：
2015-07-15
期刊：
影响因子：
16.2
通讯作者：
Woolf CJ
中科院分区：
文献类型：
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作者：
Talbot S;Abdulnour RE;Burkett PR;Lee S;Cronin SJ;Pascal MA;Laedermann C;Foster SL;Tran JV;Lai N;Chiu IM;Ghasemlou N;DiBiase M;Roberson D;Von Hehn C;Agac B;Haworth O;Seki H;Penninger JM;Kuchroo VK;Bean BP;Levy BD;Woolf CJ
肺部伤害感受器引发咳嗽和支气管收缩。为了阐明这些纤维是否也会导致过敏性气道炎症，我们用辣椒素刺激肺部伤害感受器，并观察到神经肽释放和免疫细胞浸润增加。相比之下，消融 Nav1.8+ 感觉神经元或用 QX-314（一种带电钠通道抑制剂，通过大孔离子通道进入，特异性阻断伤害感受器）沉默它们，可显着减少卵清蛋白或屋尘螨诱导的气道炎症和支气管高反应性。我们还发现，IL-5（一种由激活的免疫细胞产生的细胞因子）直接作用于伤害感受器，诱导血管活性肠肽（VIP）的释放。 VIP 然后刺激 CD4+ 和驻留的先天淋巴 2 型细胞，形成炎症信号循环，促进过敏性炎症。我们的结果表明，伤害感受器会增强病理性适应性免疫反应，而用 QX-314 沉默这些神经元会中断这种神经免疫相互作用，从而揭示了一种潜在的哮喘新治疗策略。
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 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.