中性粒细胞髓源性抑制细胞（PMN-MDSCs）在肺部构建免疫抑制微环境，并与支气管扩张症的临床结局相关。
PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis.
作者信息
Duan Jielin, Huang Zhiwen, Jiang Ying, Xian Mo, Wang Wanjun, Yang Zhaowei, Shi Xu, Jia Nan, Li Naijian, Li Bizhou, Lian Zexuan, Ning Xiaoping, Guo Yubiao, Tang Haixiong, Dong Meihua, He Li, Yang Wenqing, Mo Renke, Huang Peiying, Yang Guan, Chen Ruchong, Cheng LinLing, Li Jing
机构信息
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Respiratory and Critical Care Medicine, Dongguan Key Laboratory of Immune Inflammation and Metabolism, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.
出版信息
Respirology. 2025 Aug;30(8):715-725. doi: 10.1111/resp.70045. Epub 2025 May 4.
BACKGROUND AND OBJECTIVE
Myeloid-derived suppressor cells (MDSCs) participate in the progression of many diseases including chronic lung diseases. However, whether MDSCs are accumulated in the lung and how MDSCs orchestrate the pulmonary microenvironment in bronchiectasis remains unknown. Here, we aim to test a hypothesis that PMN-MDSCs are accumulated in the lung and play a role in creating an airway immunosuppressive milieu, thereby relating to clinical outcomes in bronchiectasis.
METHODS
Flow cytometry and immunofluorescence staining were performed for analysing the frequencies and presence of PMN-MDSCs, LOX-1 neutrophils, and ARG-1 PMN-MDSCs in PBMCs, sputum, and lung tissues. T-cell proliferation assays were established for evaluating the immunosuppressive activities of PMN-MDSCs. RNA sequencing was performed to investigate the underlying mechanism of PMN-MDSCs-mediated immunosuppression. The relationship of PMN-MDSCs with the time to next exacerbation and treatment response to antibiotic therapy was analysed.
RESULTS
PMN-MDSCs are accumulated in the lung and blood in bronchiectasis patients compared to healthy individuals. The majority of neutrophils in the lung of bronchiectasis patients are LOX-1 PMN-MDSCs. Mechanistically, PMN-MDSCs suppress T cell proliferation via secreting high levels of the enzyme arginase-1 (ARG-1). Notably, the frequencies of PMN-MDSCs in sputum negatively correlate with the time to next exacerbation in bronchiectasis patients. Additionally, antibiotic therapy dramatically decreases PMN-MDSCs frequencies in the airway of bronchiectasis patients.
CONCLUSION
These findings suggest that PMN-MDSCs accumulate and establish an immunosuppressive microenvironment in the lung via ARG-1 in bronchiectasis, which is associated with clinical outcome and response to antibiotic treatment, highlighting a potential role of PMN-MDSCs in bronchiectasis progression.
背景与目的
髓源性抑制细胞（MDSCs）参与包括慢性肺部疾病在内的多种疾病的进展。然而，MDSCs是否在肺部积聚以及它们如何在支气管扩张症中协调肺部微环境仍不清楚。在此，我们旨在验证一个假设，即多形核白细胞来源的MDSCs（PMN-MDSCs）在肺部积聚，并在营造气道免疫抑制环境中发挥作用，从而与支气管扩张症的临床结局相关。
方法
采用流式细胞术和免疫荧光染色分析外周血单个核细胞（PBMCs）、痰液和肺组织中PMN-MDSCs、凝集素样氧化低密度脂蛋白受体1（LOX-1）中性粒细胞和精氨酸酶1（ARG-1）PMN-MDSCs的频率和存在情况。建立T细胞增殖试验以评估PMN-MDSCs的免疫抑制活性。进行RNA测序以研究PMN-MDSCs介导免疫抑制的潜在机制。分析PMN-MDSCs与下次病情加重时间以及抗生素治疗反应之间的关系。
结果
与健康个体相比，支气管扩张症患者的肺部和血液中PMN-MDSCs积聚。支气管扩张症患者肺部的大多数中性粒细胞是LOX-1 PMN-MDSCs。从机制上讲，PMN-MDSCs通过分泌高水平的精氨酸酶-1（ARG-1）抑制T细胞增殖。值得注意的是，支气管扩张症患者痰液中PMN-MDSCs的频率与下次病情加重时间呈负相关。此外，抗生素治疗可显著降低支气管扩张症患者气道中PMN-MDSCs的频率。
结论
这些发现表明，在支气管扩张症中，PMN-MDSCs通过ARG-1在肺部积聚并建立免疫抑制微环境，这与临床结局和抗生素治疗反应相关，突出了PMN-MDSCs在支气管扩张症进展中的潜在作用。
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