Wang Ying, Wang Jianye, Liu Gaoyu, Yi Xianfu, Wu Jingyi, Cao Hailong, Zhang Lijuan, Zhou Pan, Fan Yong, Yu Ying, Liu Qiang, Yao Zhi, Wang Haitao, Zhou Jie
Department of oncology, The Second Hospital of Tianjin Medical University; Tianjin Key Laboratory of Precision Medicine for Sex Hormones and Diseases; Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin, China.
Cell Mol Immunol. 2025 Feb;22(2):161-175. doi: 10.1038/s41423-024-01246-7. Epub 2025 Jan 1.
Group 3 innate lymphoid cells (ILC3s) control tissue homeostasis and orchestrate mucosal inflammation; however, the precise mechanisms governing ILC3 activity are fully understood. Here, we identified the transmembrane protein neuropilin-1 (NRP1) as a positive regulator of interleukin (IL)-17-producing ILC3s in the intestine. NRP1 was markedly upregulated in intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) compared with healthy controls. Genetic deficiency of NRP1 reduces the frequency of ILC3s in the gut and impairs their production of IL-17A in an NF-κB signaling-dependent and cell-intrinsic manner. The diminished IL-17A production in ILC3s altered the composition of the microbiota and improved the outcome of dextran sodium sulfate (DSS)-induced colitis. Furthermore, pharmacological inhibition of NRP1 with EG00229 alleviated the severity of colitis. These observations demonstrated the critical role of NRP1 in the control of intestinal ILC3s, suggesting that NRP1 is a potential therapeutic target for IBD.
第3组固有淋巴细胞（ILC3s）控制组织稳态并协调黏膜炎症；然而，调控ILC3活性的精确机制尚未完全明确。在此，我们鉴定出跨膜蛋白神经纤毛蛋白-1（NRP1）是肠道中产生白细胞介素（IL）-17的ILC3s的正向调节因子。与健康对照相比，炎症性肠病（IBD）患者的肠道黏膜活检组织中NRP1明显上调。NRP1基因缺陷会降低肠道中ILC3s的频率，并以NF-κB信号依赖和细胞内在的方式损害其IL-17A的产生。ILC3s中IL-17A产生的减少改变了微生物群的组成，并改善了葡聚糖硫酸钠（DSS）诱导的结肠炎的结局。此外，用EG00229对NRP1进行药理学抑制减轻了结肠炎的严重程度。这些观察结果证明了NRP1在肠道ILC3s调控中的关键作用，表明NRP1是IBD的一个潜在治疗靶点。
