FcεR1-expressing nociceptors trigger allergic airway inflammation.
FcεR1-expressing nociceptors trigger allergic airway inflammation.
复制标题
表达fcε r1的伤害感受器引发过敏性气道炎症。
DOI：
10.1016/j.jaci.2020.12.644
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发表时间：
2021-06
影响因子：
14.2
通讯作者：
Talbot, Sebastien
中科院分区：
文献类型：
--
作者：
Crosson, Theo;Wang, Jo-Chiao;Doyle, Benjamin;Merrison, Hannah;Balood, Mohammad;Parrin, Alexandre;Pascal, Maud;Mindt, Barbara C.;Seehus, Corey R.;Ozcan, Alp;Huang, Xuan;Semenara, Elise;Lai, Nicole Y. Y.;Majdoubi, Abdelilah;Abdulnour, Raja-Elie E.;Rajchgot, Trevor;Rafei, Moutih;Foster, Simmie L.;Thibodeau, Jacques;Fritz, Joerg H.;Levy, Bruce D.;Woolf, Clifford J.;Talbot, Sebastien
关键词：
致敏小鼠肺伤害感受器神经元对吸入过敏原激发的免疫细胞活性和粘液化生的反应增强。我们现在试图确定这些感觉神经元在过敏原暴露后被激活的细胞机制。我们使用钙显微镜和电生理记录，以评估是否迷走神经元直接响应模型过敏原卵清蛋白（OVA）。接下来，我们产生了第一只伤害感受器特异性FcεR1γ敲低（TRPV 1Cre：：FcεR1γfl/fl）小鼠，以评估这种靶向失效是否会影响过敏原激发后过敏性炎症的严重程度。肺神经支配的颈静脉结状复合神经节（JNC）神经元表达高亲和力IgE受体FcεR1，并且该受体的水平在OVA致敏小鼠中增加。表达FcεR1γ的迷走伤害感受器神经元直接响应与IgE复合的OVA，具有去极化、动作电位放电、钙内流和神经肽释放。IgE/过敏原免疫复合物通过从其外周末梢释放P物质（SP）激活迷走神经元，直接放大气道中的TH 2细胞流入和极化。TRPV 1cre：：FcεR1γfl/fl小鼠或骨髓移植FcsR 1 α−/−小鼠的过敏性气道炎症减少。最后，过敏原致敏后体内循环IgE水平的增加增强了FcεR1对小鼠JNC神经元和人iPSC衍生伤害感受器中免疫复合物的反应性。过敏原致敏触发IgE产生浆细胞、表达FcεR1的迷走神经感觉神经元和TH 2细胞之间的前馈炎症循环，这有助于启动和放大过敏性气道炎症。这些数据突出了减少过敏的新靶点;由伤害感受器表达的FcεR1γ。
Lung nociceptor neurons amplify immune cell activity and mucus metaplasia in response to an inhaled allergen challenge in sensitized mice. We now sought to identify the cellular mechanisms by which these sensory neurons are activated upon allergen exposure. We used calcium microscopy and electrophysiological recording to assess whether vagal neurons directly respond to the model allergen ovalbumin (OVA). Next, we generated the first nociceptor specific FcεR1γ knockdown (TRPV1Cre::FcεR1γfl/fl) mice to assess whether this targeted invalidation would impact the severity of allergic inflammation in response to allergen challenges. Lung-innervating jugular nodose complex ganglion (JNC) neurons express the high-affinity IgE receptor FcεR1 and the levels of this receptor increase in OVA-sensitized mice. FcεR1γ-expressing vagal nociceptor neurons respond directly to OVA complexed with IgE, with depolarization, action potential firing, calcium influx, and neuropeptide release. Activation of vagal neurons by IgE/allergen immune complexes, through the release of substance P (SP) from their peripheral terminals, directly amplifies TH2 cell influx and polarization in the airways. Allergic airway inflammation is decreased in TRPV1cre::FcεR1γfl/fl mice or in bone marrow-transplanted FcsR1α−/− mice. Finally, increased in vivo circulating levels of IgE following allergen sensitization enhances the responsiveness of FcεR1 to immune complexes in both mouse JNC neurons and human iPSC-derived nociceptors. Allergen-sensitization triggers a feedforward inflammatory loop between IgE-producing plasma cells, FcεR1 expressing vagal sensory neurons, and TH2 cells, which helps both initiate and amplify allergic airway inflammation. These data highlight a novel target for reducing allergy; FcεR1γ expressed by nociceptors.
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影响因子：
7.3
作者：
Foster SL;Seehus CR;Woolf CJ;Talbot S
通讯作者：
Talbot S
DOI：
10.1016/j.jpain.2014.09.010
发表时间：
2014-12
期刊：
The journal of pain
影响因子：
--
作者：
Goswami SC;Mishra SK;Maric D;Kaszas K;Gonnella GL;Clokie SJ;Kominsky HD;Gross JR;Keller JM;Mannes AJ;Hoon MA;Iadarola MJ
通讯作者：
Iadarola MJ
影响因子：
3.3
作者：
CONTI, G;VEDELER, C;PLEASURE, D
通讯作者：
PLEASURE, D
影响因子：
4.4
作者：
Hsu, C;MacGlashan, D
通讯作者：
MacGlashan, D
影响因子：
4.4
作者：
Harada, Naoaki;Zhao, Juan;Okajima, Kenji
通讯作者：
Okajima, Kenji