2型细胞因子作用于肠感觉神经元，调节神经肽驱动的宿主防御，这一成果由
研究组鉴定了一个初级肠感觉神经元（PSN）亚群，产生神经肽神经素U （NMU）和降钙素基因相关肽β (CGRPβ)，并共同表达2型细胞因子白介素-4 （IL-4）和IL-13受体。2型细胞因子在体外和体内均能扩增PSN中NMU和CGRPβ的表达，而这种表达被PSN特异性Il13ra1缺失所消除。PSN中Il13ra1的缺失损害了宿主对胃肠道蠕虫多旋Heligmosomoides polygyrthem的防御，并减弱了免疫反应。同时给药NMU23和CGRPβ可挽救蠕虫清除缺陷并恢复抗蠕虫免疫，突出了调节肠道2型炎症的重要双向神经免疫串音。
据悉，肠神经系统（ENS）衍生的神经肽调节免疫细胞功能，但它们对炎症线索如何直接影响感染期间肠神经元反应的理解相当缺乏。
附：英文原文
Title: Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense
Author: Rocky M. Barilla, Clara Berard, Linyu Sun, Sumiti Sandhu, Sarah Zaghouani, Krishna S. Iyer, Gizem Altun, Chien-Wen Su, Jacques Deguine, Vasundhara Singh, Yu Hou, Kanupriya Kusumakar, Michael L. Rutlin, Meenakshi Rao, Habib Zaghouani, Hai Ning Shi, Ramnik J. Xavier, Vijay K. Kuchroo
Issue&Volume: 2025-05-22
Abstract: Enteric nervous system (ENS)–derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is considerably lacking. Here, we characterized a primary enteric sensory neuron (PSN) subset producing the neuropeptides neuromedin U (NMU) and calcitonin gene-related peptide β (CGRPβ) and coexpressing receptors for the type 2 cytokines interleukin-4 (IL-4) and IL-13. Type 2 cytokines amplified NMU and CGRPβ expression in PSNs, in vitro and in vivo, which was abrogated by PSN-specific Il13ra1 deletion. Deletion of Il13ra1 in PSNs impaired host defense to the gastrointestinal helminth Heligmosomoides polygyrus and blunted muscularis immune responses. Co-administration of NMU23 and CGRPβ rescued helminth clearance deficits and restored anti-helminth immunity, highlighting the essential bi-directional neuro-immune crosstalk regulating intestinal type 2 inflammation.
DOI: adn9850
Source: https://www.science.org/doi/10.1126/science.adn9850