Yu Xinhua, Yue Xiaoyang, Tchudjin Magatsin Junie D, Marwitz Sebastian, Behrends Jochen, Goldmann Torsten, Opferman Joseph T, Kasper Brigitte, Petersen Frank
Research Center Borstel, Leibniz Lung Center, Priority Area Chronic Lung Disease, Members of the German Center for Lung Research (DZLARCN), Borstel, Germany.
Key Laboratory of Basic Research on Regional Diseases, Education Department of Guangxi Zhuang Autonomous Region, College of Basic Medical Science, Guangxi Medical University, Nanning, Guangxi, China.
Front Immunol. 2025 Mar 20;16:1542191. doi: 10.3389/fimmu.2025.1542191. eCollection 2025.
In addition to serving as the primary effector cells against infections, neutrophils have been implicated in the regulation of both innate and adaptive immunity. In this study, we aimed to investigate the role of neutrophils in the regulation of the immune system under physiological conditions.
The effect of neutrophils on the immune system was examined using neutropenic mice. The interaction between neutrophils and γδ T cells was investigated using an co-culture system.
Unexpectedly, we observed an accumulation of γδ T cells in the cervical lymph nodes of neutropenic mice. Transcriptomic analysis revealed that these γδ T cells exhibited unique expression profiles of cell surface molecules and genes involved in defense responses. Further characterization indicated that the accumulated γδ T cells were IL-17 producing CD44CD62LCD27 memory cells. Additionally, experiments demonstrated that neutrophils could inhibit the function of IL-17A producing γδ T cells by inducing cell death in a contact-dependent manner.
This present study demonstrates that neutrophils negatively regulate IL-17 producing γδ T cells under physiological conditions. Given that IL-17A is a critical cytokine for the recruitment of neutrophils to peripheral tissues, our study suggests that the crosstalk between neutrophils and IL-17A producing γδ T cells is a crucial mechanism for maintaining immune homeostasis under physiological conditions.
除了作为抵抗感染的主要效应细胞外，中性粒细胞还参与了固有免疫和适应性免疫的调节。在本研究中，我们旨在探究中性粒细胞在生理条件下对免疫系统调节中的作用。
使用中性粒细胞减少的小鼠来检测中性粒细胞对免疫系统的影响。利用共培养系统研究中性粒细胞与γδT细胞之间的相互作用。
出乎意料的是，我们在中性粒细胞减少的小鼠颈部淋巴结中观察到γδT细胞的聚集。转录组分析显示，这些γδT细胞表现出参与防御反应的细胞表面分子和基因的独特表达谱。进一步的特征分析表明，聚集的γδT细胞是产生IL-17的CD44⁺CD62L⁻CD27⁺记忆细胞。此外，实验证明中性粒细胞可通过接触依赖性诱导细胞死亡来抑制产生IL-17A的γδT细胞的功能。
本研究表明，中性粒细胞在生理条件下对产生IL-17的γδT细胞具有负向调节作用。鉴于IL-17A是将中性粒细胞募集到外周组织的关键细胞因子，我们的研究表明中性粒细胞与产生IL-17A的γδT细胞之间的相互作用是在生理条件下维持免疫稳态的关键机制。
