David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusetts, USA.
JCI Insight. 2021 Dec 22;6(24):e148510. doi: 10.1172/jci.insight.148510.
Nociceptors, the high-threshold primary sensory neurons that trigger pain, interact with immune cells in the periphery to modulate innate immune responses. Whether they also participate in adaptive and humoral immunity is, however, not known. In this study, we probed if nociceptors have a role in distinct airway and skin models of allergic inflammation. In both models, the genetic ablation and pharmacological silencing of nociceptors substantially reduced inflammatory cell infiltration to the affected tissue. Moreover, we also found a profound and specific deficit in IgE production in these models of allergic inflammation. Mechanistically, we discovered that the nociceptor-released neuropeptide substance P helped trigger the formation of antibody-secreting cells and their release of IgE. Our findings suggest that nociceptors, in addition to their contributions to innate immunity, play a key role in modulating the adaptive immune response, particularly B cell antibody class switching to IgE.
伤害感受器是触发疼痛的高阈值初级感觉神经元，它们与外周的免疫细胞相互作用，调节先天免疫反应。然而，它们是否也参与适应性和体液免疫尚不清楚。在这项研究中，我们探讨了伤害感受器是否在不同的气道和皮肤过敏性炎症模型中发挥作用。在这两种模型中，伤害感受器的基因缺失和药理学沉默都显著减少了炎症细胞向受影响组织的浸润。此外，我们还发现，在这些过敏性炎症模型中，IgE 的产生也存在明显而特异的缺陷。从机制上讲，我们发现伤害感受器释放的神经肽 P 物质有助于触发抗体分泌细胞的形成及其 IgE 的释放。我们的研究结果表明，伤害感受器除了对先天免疫有贡献外，还在调节适应性免疫反应中发挥关键作用，特别是 B 细胞抗体类别转换为 IgE。
