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支配各种组织，以持续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的免疫反应，目前尚不明确。在这里，我们证实痛觉神经纤维沿血管广泛支配脾脏并到达B细胞区。支配脾脏的痛觉感受器主要起源于左侧 T8-T13 背根神经节（DRGs），可促进脾脏生殖中心（GC）反应和体液免疫。痛觉感受器可被抗原诱导的脾脏前列腺素 E2（PGE2）积聚激活，然后释放降钙素基因相关肽（CGRP），进一步促进脾脏的早期GC反应。从机理上讲，CGRP通过其受体CALCRL-RAMP1经环状 AMP（cAMP）信号通路直接作用于B细胞。通过摄入辣椒素激活痛觉感受器可增强脾脏GC反应和抗流感免疫力。总之，我们的研究建立了一种促进体液免疫的特异性DRG-脾感觉神经联系，为通过靶向痛觉神经系统提高宿主防御能力提供了一种可行的方法。
参考文献
Wu M, Song G, Li J, Song Z, Zhao B, Liang L, Li W, Hu H, Tu H, Li S, Li P, Zhang B, Wang W, Zhang Y, Zhang W, Zheng W, Wang J, Wen Y, Wang K, Li A, Zhou T, Zhang Y, Li H. Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity. Cell. 2024 Jun 6;187(12):2935-2951.e19. doi: 10.1016/j.cell.2024.04.027.
