美国威尔康奈尔医学院David Artis团队近期取得重要工作进展，他们研究发现了神经肽对屏障表面非冗余ILC2应答反应的调节。相关研究成果2022年11月2日在线发表于《自然》杂志上。

研究人员开发了一种新的基因工具，在完整适应性免疫系统存在的情况下，针对ILC2进行耗尽或基因删除。在小鼠Nmur1启动子的调控下，iCre重组酶的转基因表达使ILC2特异性缺失AREG。这表明ILC2来源的AREG在抗寄生虫免疫、肠道损伤及炎症后组织保护方面促进非冗余功能。NMU在小鼠和人类发炎的肠道组织中表达水平增加，NMU诱导小鼠和人类ILC2产生AREG。结果表明，神经肽介导的ILC2非冗余功能调控是一种整合免疫和组织保护的进化保守机制。

据介绍，新的研究表明，神经元和免疫细胞共同合作调节抗微生物免疫、炎症和组织内稳态。例如，神经元变阻器提供兴奋或抑制信号，控制粘膜屏障表面组织驻留的第2组先天淋巴细胞（ILC2）功能。ILC2表达NMUR1，NMUR1是神经介质U（NMU）的受体，这是一种突出的胆碱能神经肽，可促进ILC2的应答反应。然而，ILC2的许多功能是与适应性淋巴细胞共享的，包括产生2型细胞因子和释放组织保护型双调节蛋白（AREG）。因此，先天淋巴细胞和适应性淋巴细胞是否具有冗余或非冗余功能目前还存在争议。

附：英文原文

Title: Neuropeptide regulation of non-redundant ILC2 responses at barrier surfaces

Author: Tsou, Amy M., Yano, Hiroshi, Parkhurst, Christopher N., Mahlakiv, Tanel, Chu, Coco, Zhang, Wen, He, Zhengxiang, Jarick, Katja J., Zhong, Connie, Putzel, Gregory G., Hatazaki, Mai, Lorenz, Ivo C., Andrew, David, Balderes, Paul, Klose, Christoph S. N., Lira, Sergio A., Artis, David

Issue&Volume: 2022-11-02

Abstract: Emerging studies indicate that cooperation between neurons and immune cells regulates antimicrobial immunity, inflammation and tissue homeostasis. For example, a neuronal rheostat provides excitatory or inhibitory signals that control the functions of tissue-resident group2 innate lymphoid cells (ILC2s) at mucosal barrier surfaces1,2,3,4. ILC2s express NMUR1, a receptor for neuromedinU (NMU), which is a prominent cholinergic neuropeptide that promotes ILC2 responses5,6,7. However, many functions of ILC2s are shared with adaptive lymphocytes, including the production of type2 cytokines8,9 and the release of tissue-protective amphiregulin (AREG)10,11,12. Consequently, there is controversy regarding whether innate lymphoid cells and adaptive lymphocytes perform redundant or non-redundant functions13,14,15. Here we generate a new genetic tool to target ILC2s for depletion or gene deletion in the presence of an intact adaptive immune system. Transgenic expression of iCre recombinase under the control of the mouse Nmur1 promoter enabled ILC2-specific deletion of AREG. This revealed that ILC2-derived AREG promotes non-redundant functions in the context of antiparasite immunity and tissue protection following intestinal damage and inflammation. Notably, NMU expression levels increased in inflamed intestinal tissues from both mice and humans, and NMU induced AREG production in mouse and human ILC2s. These results indicate that neuropeptide-mediated regulation of non-redundant functions of ILC2s is an evolutionarily conserved mechanism that integrates immunity and tissue protection.

DOI: 10.1038/s41586-022-05297-6

Source: https://www.nature.com/articles/s41586-022-05297-6