在脓毒症患者中，中性粒细胞通过精氨酸酶-1信号传导抑制CD8 T细胞免疫反应。
Neutrophils inhibit CD8 T cells immune response by arginase-1 signaling in patients with sepsis.
作者信息
Dai Xiao-Kang, Ding Zhen-Xing, Tan Yuan-Yuan, Bao Hua-Rui, Wang Dong-Yao, Zhang Hong
机构信息
Department of Emergency, the First Affiliated Hospital of Anhui Medical University, Hefei 230027, China.
Department of Hematology, the First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, Hefei 230001, China.
出版信息
World J Emerg Med. 2022;13(4):266-273. doi: 10.5847/wjem.j.1920-8642.2022.068.
BACKGROUND
Patients with sepsis often exhibit an acute inflammatory response, followed by an immunosuppressive phase with a poor immune response. However, the underlying mechanisms have not been fully elucidated.
METHODS
We sought to comprehensively characterize the transcriptional changes in neutrophils of patients with sepsis by transcriptome sequencing. Additionally, we conducted a series of experiments, including real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry to investigate the role of arginase-1 signaling in sepsis.
RESULTS
Through the analysis of gene expression profiles, we identified that the negative regulation of T cell activation signaling was enriched, and the expression of arginase-1 was high in neutrophils from patients with sepsis. Furthermore, we conducted flow cytometry and found that the function of CD8 T cells in septic patients was impaired. Moreover, neutrophils from septic patients inhibited the percentage of polyfunctional effector CD8 T cells through arginase-1. Additionally, the proportions of granzyme BIFNγCD8 T and TNFαIFNγCD8 T cells increased after inhibition of arginase-1 signaling.
CONCLUSION
The impaired effector function of CD8 T cells could be restored by blocking arginase-1 signaling in patients with sepsis.
背景
脓毒症患者常表现出急性炎症反应，随后进入免疫抑制阶段，免疫反应较差。然而，其潜在机制尚未完全阐明。
方法
我们试图通过转录组测序全面表征脓毒症患者中性粒细胞的转录变化。此外，我们进行了一系列实验，包括实时定量聚合酶链反应（RT-qPCR）和流式细胞术，以研究精氨酸酶-1信号在脓毒症中的作用。
结果
通过基因表达谱分析，我们发现T细胞活化信号的负调控得到富集，脓毒症患者中性粒细胞中精氨酸酶-1的表达较高。此外，我们进行了流式细胞术，发现脓毒症患者中CD8 T细胞的功能受损。此外，脓毒症患者的中性粒细胞通过精氨酸酶-1抑制多功能效应CD8 T细胞的百分比。此外，抑制精氨酸酶-1信号后，颗粒酶B IFNγ CD8 T细胞和TNFα IFNγ CD8 T细胞的比例增加。
结论
在脓毒症患者中，通过阻断精氨酸酶-1信号可恢复CD8 T细胞受损的效应功能。
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