近日，国家生物医学分析中心南湖实验室李慧艳等研究人员合作发现，脾脏伤害性感受神经元的神经支配促进生发中心反应和体液免疫。这一研究成果于2024年5月20日在线发表在国际学术期刊《细胞》上。
研究人员证明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（DRG），可促进脾脏生发中心（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经环化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，该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。
据悉，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免疫反应仍不清楚。
附：英文原文
Title: Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity
Author: Min Wu, Guangping Song, Jianing Li, Zengqing Song, Bing Zhao, Liyun Liang, Wenlong Li, Huaibin Hu, Haiqing Tu, Sen Li, Peiyao Li, Biyu Zhang, Wen Wang, Yu Zhang, Wanpeng Zhang, Weifan Zheng, Jiarong Wang, Yuqi Wen, Kai Wang, Ailing Li, Tao Zhou, Yucheng Zhang, Huiyan Li
Issue&Volume: 2024-05-20
Abstract: Peripheral sensory neurons widely innervate various tissues to continuously monitorand respond to environmental stimuli. Whether peripheral sensory neurons innervatethe spleen and modulate splenic immune response remains poorly defined. Here, we demonstratethat nociceptive sensory nerve fibers extensively innervate the spleen along bloodvessels and reach B cell zones. The spleen-innervating nociceptors predominantly originatefrom left T8–T13 dorsal root ganglia (DRGs), promoting the splenic germinal center(GC) response and humoral immunity. Nociceptors can be activated by antigen-inducedaccumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotesthe splenic GC response at the early stage. Mechanistically, CGRP directly acts onB cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway.Activating nociceptors by ingesting capsaicin enhances the splenic GC response andanti-influenza immunity. Collectively, our study establishes a specific DRG-spleensensory neural connection that promotes humoral immunity, suggesting a promising approachfor improving host defense by targeting the nociceptive nervous system.
DOI: 10.1016/j.cell.2024.04.027
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00453-7