Xu Hongkai, Wang Yibo, Wang Wenyan, Fu Yang-Xin, Qiu Ju, Shi Yan, Yuan Lei, Dong Chen, Hu Xiaoyu, Chen Ye-Guang, Guo Xiaohuan
Institute for Immunology, Tsinghua University, Beijing 100084, China.
School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing 100084, China.
Sci Immunol. 2025 May 16;10(107):eadn1491. doi: 10.1126/sciimmunol.adn1491.
Helminth infections, particularly in developing countries, remain a notable health burden worldwide. Group 3 innate lymphoid cells (ILC3s) are enriched in the intestine and play a critical role in immunity against extracellular bacteria and fungi. However, whether ILC3s are involved in intestinal helminth infection is still unclear. Here, we report that helminth infection reprograms ILC3s, which, in turn, promote anthelmintic immunity. ILC3-derived RANKL [receptor activator of NF-κB (nuclear factor κB) ligand] synergizes with interleukin-13 (IL-13) to facilitate intestinal tuft cell expansion after helminth infection, which further activates the tuft cell-group 2 innate lymphoid cell (ILC2) circuit to control helminth infection. Deletion of RANKL in ILC3s or deletion of RANK or its downstream adaptor RelB in intestinal epithelial cells substantially diminishes tuft cell hyperplasia and dampens anthelmintic immunity. Thus, ILC3s play an indispensable role in protecting against helminth infection through the regulation of intestinal tuft cell hyperplasia and type 2 immunity.
蠕虫感染，尤其是在发展中国家，仍然是全球范围内一个显著的健康负担。3型天然淋巴细胞（ILC3s）在肠道中富集，并在抵抗细胞外细菌和真菌的免疫中发挥关键作用。然而，ILC3s是否参与肠道蠕虫感染仍不清楚。在此，我们报告蠕虫感染会对ILC3s进行重编程，进而促进抗蠕虫免疫。ILC3s衍生的RANKL [核因子κB（NF-κB）受体激活剂配体] 与白细胞介素-13（IL-13）协同作用，以促进蠕虫感染后肠道簇状细胞的扩增，这进一步激活了簇状细胞-2型天然淋巴细胞（ILC2）回路来控制蠕虫感染。在ILC3s中删除RANKL或在肠道上皮细胞中删除RANK或其下游衔接蛋白RelB，会显著减少簇状细胞增生并削弱抗蠕虫免疫。因此，ILC3s通过调节肠道簇状细胞增生和2型免疫，在预防蠕虫感染中发挥不可或缺的作用。
