德国柏林自由大学Christoph S. N. Klose团队揭示第2组先天性淋巴细胞的非冗余功能。2022年11月2日，《自然》杂志在线发表了这项成果。

研究人员表示，保护性免疫依赖于具有互补和冗余功能的先天和适应性免疫细胞的相互作用。先天性淋巴细胞（ILC）最近被认为是T细胞系统的组织驻留的先天性镜像，它们与T细胞系统有共同的谱系特化转录因子和效应机制。位于屏障表面的ILC是对入侵病原体的第一反应者之一，因此有可能决定免疫反应的结果。然而，到目前为止，由于ILC亚群的特异性目标的限制，还不可能剖析ILC对保护性免疫的独特贡献。因此，所有可用的数据都是在缺乏适应性免疫系统的小鼠中产生的，或者是用也影响其他免疫细胞亚群的工具。此外，有人提出ILC对于适当的免疫反应可能是可有可无的，因为其他免疫细胞可以补偿它们的缺失。

研究人员报告了基于神经介素U受体1（Nmur1）启动子的小鼠模型构建，其作为同时表达Cre重组酶和绿色荧光蛋白的驱动因素，这使得基因靶向在第二组ILC（ILC2）而不影响其他先天和适应性免疫细胞。利用Cre介导的Id2和Gata3在Nmur1表达细胞中的基因缺失，研究人员产生了ILC2的选择性和特异性缺陷的小鼠。ILC2缺陷的小鼠在稳定状态下嗜酸性粒细胞数量减少，在过敏性哮喘的模型中不能招募嗜酸性粒细胞到气道。此外，ILC2缺陷的小鼠不能产生适当的免疫和上皮2型反应，导致排虫的严重缺陷和非保护性3型免疫反应。

总之，这些数据确立了ILC2在适应性免疫细胞存在的稳定状态和疾病期间的非冗余功能，并论证了免疫系统在时空分工基础上的多层次组织。

附：英文原文

Title: Non-redundant functions of group 2 innate lymphoid cells

Author: Jarick, Katja J., Topczewska, Patrycja M., Jakob, Manuel O., Yano, Hiroshi, Arifuzzaman, Mohammad, Gao, Xuemei, Boulekou, Sotiria, Stokic-Trtica, Vladislava, Leclre, Pierre S., Preuer, Alexandra, Rompe, Zoe A., Stamm, Anton, Tsou, Amy M., Chu, Coco, Heinrich, Frederik R., Guerra, Gabriela M., Durek, Pawel, Ivanov, Andranik, Beule, Dieter, Helfrich, Sofia, Duerr, Claudia U., Khl, Anja A., Stehle, Christina, Romagnani, Chiara, Mashreghi, Mir-Farzin, Diefenbach, Andreas, Artis, David, Klose, Christoph S. N.

Issue&Volume: 2022-11-02

Abstract: Protective immunity relies on the interplay of innate and adaptive immune cells with complementary and redundant functions. Innate lymphoid cells (ILCs) have recently emerged as tissue-resident, innate mirror images of the T cell system, with which they share lineage-specifying transcription factors and effector machinery1. Located at barrier surfaces, ILCs are among the first responders against invading pathogens and thus could potentially determine the outcome of the immune response2. However, so far it has not been possible to dissect the unique contributions of ILCs to protective immunity owing to limitations in specific targeting of ILC subsets. Thus, all of the available data have been generated either in mice lacking the adaptive immune system or with tools that also affect other immune cell subsets. In addition, it has been proposed that ILCs might be dispensable for a proper immune response because other immune cells could compensate for their absence3,4,5,6,7. Here we report the generation of a mouse model based on the neuromedin U receptor 1 (Nmur1) promoter as a driver for simultaneous expression of Cre recombinase and green fluorescent protein, which enables gene targeting in group 2 ILCs (ILC2s) without affecting other innate and adaptive immune cells. Using Cre-mediated gene deletion of Id2 and Gata3 in Nmur1-expressing cells, we generated mice with a selective and specific deficiency in ILC2s. ILC2-deficient mice have decreased eosinophil counts at steady state and are unable to recruit eosinophils to the airways in models of allergic asthma. Further, ILC2-deficient mice do not mount an appropriate immune and epithelial type 2 response, resulting in a profound defect in worm expulsion and a non-protective type 3 immune response. In total, our data establish non-redundant functions for ILC2s in the presence of adaptive immune cells at steady state and during disease and argue for a multilayered organization of the immune system on the basis of a spatiotemporal division of labour.

DOI: 10.1038/s41586-022-05395-5

Source: https://www.nature.com/articles/s41586-022-05395-5