Abstract
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.
摘要
屏障组织的免疫反应部分由伤害感受器（痛觉感受器）调控。伤害感受器的去除会改变外周部位及其引流淋巴结（LNs）中的局部免疫反应。然而，伤害感受器依赖的淋巴结功能调节机制及其意义尚不清楚。通过高分辨率成像、病毒追踪、单细胞转录组学和光遗传学，我们鉴定并功能性验证了一个对淋巴源性炎症信号有反应的感觉神经-免疫回路。转录组学分析显示，多种感觉神经元亚群，主要是肽能伤害感受器，支配了淋巴结，这与支配周围皮肤的神经元不同。为了揭示可能与支配淋巴结的感觉神经元相互作用的淋巴结驻留细胞，我们生成了一个淋巴结单细胞转录组图谱，推测了伤害感受器的靶细胞群体及其相互作用方式。光遗传学刺激支配淋巴结的感觉纤维引发了预测的相互作用细胞类型，特别是内皮细胞、基质细胞和先天性白细胞的快速转录变化。因此，一群特定的感觉神经元监测外周淋巴结，并可能在局部调控基因表达。
