美国耶鲁大学医学院Richard A. Flavell和哈佛医学院布莱根妇女医院Roni Nowarski研究组合作，发现肠神经系统分泌的IL-18介导粘膜免屏障。2020年1月9日，国际学术期刊《细胞》在线发表了这一成果。
尽管免疫细胞和上皮细胞被认为是体内复杂平衡的典型协调者，但在这项研究中，研究人员发现肠神经系统（ENS）在控制抗菌蛋白（AMP）反应中起着至关重要的作用。利用共聚焦显微镜和单分子荧光原位mRNA杂交（smFISH）的方法，研究人员发现肠神经元产生多效性细胞因子IL-18。令人意外的是，仅在肠神经元中缺失IL-18，而不是免疫或上皮细胞IL18缺失，会使小鼠容易受到侵袭性鼠伤寒沙门氏菌（S.t.）的感染。无偏倚RNA测序和单细胞测序表明，肠内神经元IL-18对于杯状细胞AMP的恒定产生是必需的。这些结果表明神经元来源的IL-18信号控制组织范围的肠道免疫，并对粘膜屏障和侵袭性细菌杀伤具有重要的作用。
据了解，黏膜屏障免疫对于维持共生菌群和抵抗侵入性细菌感染至关重要。
附：英文原文
Title: Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity
Author: Abigail Jarret, Ruaidhrí Jackson, Coco Duizer, Marc E. Healy, Jun Zhao, Joseph M. Rone, Piotr Bielecki, Esen Sefik, Manolis Roulis, Tyler Rice, Kisha N. Sivanathan, Ting Zhou, Angel G. Solis, Hanna Honcharova-Biletska, Karelia Vélez, Saskia Hartner, Jun Siong Low, Rihao Qu, Marcel R. de Zoete, Noah W. Palm, Aaron M. Ring, Achim Weber, Andreas E. Moor, Yuval Kluger, Roni Nowarski, Richard A. Flavell
Issue&Volume: 2020/01/09
Abstract: Mucosal barrier immunity is essential for the maintenance of the commensal microfloraand combating invasive bacterial infection. Although immune and epithelial cells arethought to be the canonical orchestrators of this complex equilibrium, here, we showthat the enteric nervous system (ENS) plays an essential and non-redundant role ingoverning the antimicrobial protein (AMP) response. Using confocal microscopy andsingle-molecule fluorescence in situ mRNA hybridization (smFISH) studies, we observed that intestinal neurons producethe pleiotropic cytokine IL-18. Strikingly, deletion of IL-18 from the enteric neuronsalone, but not immune or epithelial cells, rendered mice susceptible to invasive Salmonella typhimurium (S.t.) infection. Mechanistically, unbiased RNA sequencing and single-cell sequencingrevealed that enteric neuronal IL-18 is specifically required for homeostatic gobletcell AMP production. Together, we show that neuron-derived IL-18 signaling controlstissue-wide intestinal immunity and has profound consequences on the mucosal barrierand invasive bacterial killing.
DOI: 10.1016/j.cell.2019.12.016
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31378-9