Neutrophils in nasal polyps exhibit transcriptional adaptation and proinflammatory role depend on local polyp milieu.

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL JCI insight Pub Date : 2024-10-03 DOI:10.1172/jci.insight.184739
Chen Zhang, Qianqian Zhang, Jiani Chen, Han Li, Fuying Cheng, Yizhang Wang, Yingqi Gao, Yumin Zhou, Le Shi, Yufei Yang, Juan Liu, Kai Xue, Yaguang Zhang, Hongmeng Yu, Dehui Wang, Li Hu, Huan Wang, Xicai Sun
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Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory upper airway disease, divided into eosinophilic CRSwNP (eCRSwNP) and noneosinophilic CRSwNP (neCRSwNP) according to eosinophilic levels. Neutrophils are major effector cells in CRSwNP. but their role in different inflammatory environments remain largely unclear. We performed an integrated transcriptome analysis of polyp-infiltrating neutrophils from CRSwNP patients, using healthy donor blood as a control. Flow cytometry and in vitro studies showed that neutrophils are activated in both CRSwNP type. The scRNA-sequencing analysis demonstrated that neutrophils were classified into five functional subsets, with GBP5+ neutrophils occurring mainly in neCRSwNPs and a high proportion of CXCL8+ neutrophils in both subendotypes. GBP5+ neutrophils exhibited significant IFN-I pathway activity in neCRSwNPs. CXCL8+ neutrophils displayed increased neutrophil activation scores and mainly secrete Oncostatin M (OSM), which facilitates communication with other cells. In vitro experiments revealed that OSM could enhance IL-13- or IL-17-mediated immune responses in nasal epithelial cells and fibroblasts. Our findings revealed that neutrophils exhibited transcriptional plasticity and activation when exposed to polyp tissue and exert their proinflammatory role in the pathogenesis of CRSwNP by releasing OSM to interact with epithelial cells and fibroblasts in a manner dependent on the inflammatory milieu.

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鼻息肉中的中性粒细胞表现出转录适应性,其促炎作用取决于当地息肉环境。
慢性鼻炎伴鼻息肉(CRSwNP)是一种上气道炎症性疾病,根据嗜酸性粒细胞水平分为嗜酸性鼻炎伴鼻息肉(eCRSwNP)和非嗜酸性鼻炎伴鼻息肉(neCRSwNP)。中性粒细胞是 CRSwNP 的主要效应细胞,但它们在不同炎症环境中的作用在很大程度上仍不清楚。我们以健康供血为对照,对 CRSwNP 患者息肉浸润中性粒细胞进行了综合转录组分析。流式细胞术和体外研究表明,CRSwNP 两种类型的中性粒细胞均被激活。scRNA 序列分析表明,中性粒细胞被分为五个功能亚群,其中 GBP5+ 中性粒细胞主要出现在 neCRSwNPs 中,两种亚型中都有很高比例的 CXCL8+ 中性粒细胞。GBP5+ 中性粒细胞在 neCRSwNPs 中表现出显著的 IFN-I 通路活性。CXCL8+嗜中性粒细胞的嗜中性粒细胞活化评分增加,并主要分泌Oncostatin M(OSM),OSM可促进与其他细胞的交流。体外实验显示,OSM 可增强鼻腔上皮细胞和成纤维细胞中 IL-13 或 IL-17 介导的免疫反应。我们的研究结果表明,中性粒细胞暴露于息肉组织时表现出转录可塑性和活化,并通过释放 OSM 与上皮细胞和成纤维细胞相互作用,以一种依赖于炎症环境的方式在 CRSwNP 的发病机制中发挥促炎作用。
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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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