Abstract：
Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.
摘要：
外周感觉神经元广泛地支配各种组织以连续地监测和响应环境刺激。外周感觉神经元是否支配脾脏并调节脾脏免疫反应尚不清楚。这里,我们证明伤害性感觉神经纤维沿血管广泛支配脾脏并到达B细胞区。脾脏神经支配的伤害感受器主要起源于左T8-T13背根神经节（DRGs），促进脾生发中心（GC）反应和体液免疫。可以通过抗原诱导的脾前列腺素E2（PGE2）的积累激活受体，然后释放降钙素基因相关肽（CGRP），进一步促进早期脾GC反应。机械上,CGRP通过其受体CALCRL-RAMP1通过环AMP（cAMP）信号通路直接作用于B细胞。通过摄入辣椒素激活伤害感受器增强脾GC应答和抗流感免疫。总的来说，我们的研究建立了促进体液免疫的特定DRG-脾感觉神经连接，提出了一种通过靶向伤害性神经系统来改善宿主防御的有希望的方法。
