Barrier tissue immune responses are regulated in part by nociceptors. Nociceptor ablation alters local immune responses at peripheral sites and within draining lymph nodes (LNs). The mechanisms and significance of nociceptor-dependent modulation of LN function are unknown. Using high-resolution imaging, viral tracing, single-cell transcriptomics, and optogenetics, we identified and functionally tested a sensory neuro-immune circuit that is responsive to lymph-borne inflammatory signals. Transcriptomics profiling revealed that multiple sensory neuron subsets, predominantly peptidergic nociceptors, innervate LNs, distinct from those innervating surrounding skin. To uncover LN-resident cells that may interact with LN-innervating sensory neurons, we generated a LN single-cell transcriptomics atlas and nominated nociceptor target populations and interaction modalities. Optogenetic stimulation of LN-innervating sensory fibers triggered rapid transcriptional changes in the predicted interacting cell types, particularly endothelium, stromal cells, and innate leukocytes. Thus, a unique population of sensory neurons monitors peripheral LNs and may locally regulate gene expression.

屏障组织免疫反应部分受伤害感受器的调节。伤害感受器消融会改变外周部位和引流淋巴结 (LN) 内的局部免疫反应。伤害感受器依赖性调节 LN 功能的机制和意义尚不清楚。使用高分辨率成像、病毒追踪、单细胞转录组学和光遗传学，我们确定并在功能上测试了一种对淋巴传播的炎症信号有反应的感觉神经免疫回路。转录组学分析显示，多个感觉神经元亚群，主要是肽能伤害感受器，支配 LN，与支配周围皮肤的那些不同。为了发现可能与 LN 支配感觉神经元相互作用的 LN 驻留细胞，我们生成了一个 LN 单细胞转录组学图谱，并指定了伤害感受器目标群体和交互方式。LN-innervating 感觉纤维的光遗传学刺激触发了预测的相互作用细胞类型的快速转录变化，特别是内皮细胞、基质细胞和先天性白细胞。因此，一组独特的感觉神经元监测外周 LN，并可能局部调节基因表达。