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EcN-Sj16-Exo ameliorates experimental asthma by inhibiting eosinophil extracellular traps formation via N-WASP upregulation. EcN-Sj16-Exo通过上调N-WASP抑制嗜酸性粒细胞胞外陷阱形成,改善实验性哮喘。
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-19 DOI: 10.1183/13993003.00948-2025
Xi Sun, Yao Liao, Ji Wu, Yuheng Liu, Dinghao Li, Zifeng Zhu, Yun Huang, Junwei Wu, Peiying Peng, Jin Su, Yingxin He, Mengxi Yanglan, Haiyi Deng, Feiyang Cao, Junhao Xu, Zhongdao Wu, Lifu Wang

Background: Eosinophilic inflammation is a feature of allergic asthma, with eosinophil depletion shown to alleviate symptoms. Elevated levels of eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid (BALF) correlate with asthma severity. Sj16 is a protein from Schistosoma japonicum with known immunoregulatory properties. Exosomes, with their protective phospholipid bilayer, serve as efficient drug carriers.

Methods: We extracted exosomes secreted by Escherichia coli Nissle 1917 engineered to express Sj16 (EcN-Sj16-Exo), and sought to investigate the role of EcN-Sj16-Exo on asthma. In ovalbumin (OVA)-induced experimental asthma model in mice, EET levels were elevated. The experimental asthma model was treated with EcN-Sj16-Exo. EET formation was assessed using immunofluorescence and scanning electron microscopy. Lung function, airway remodeling, and inflammatory were evaluated. Wiskott-Aldrich syndrome-like (WASL) knockout mice and recombinant adeno-associated virus (rAAV)-expressing Neural Wiskott-Aldrich syndrome protein (N-WASP) were used to investigate the potential mechanisms of EcN-Sj16-Exo.

Results: EET formation was increased in sputum and BALF from asthma patients. We demonstrate that Sj16 inhibits EET formation in vitro and localizes primarily in exosomes when secreted by EcN-Sj16. In the experimental asthma model, EcN-Sj16-Exo significantly reduced EET formation. Moreover, EcN-Sj16-Exo significantly attenuated airway hyperreactivity (AHR) and airway remodeling, as evidenced by reduced lung resistance (RL), improved dynamic compliance (Cdyn), and diminished inflammatory cell infiltration, fibrosis, and mucus hypersecretion. Furthermore, EcN-Sj16-Exo decreased eosinophil and neutrophil counts, IgE, and type 2 cytokines levels in BALF while increasing Treg cells in the spleen. Mechanistically, EcN-Sj16-Exo inhibited EET formation by upregulating N-WASP. WASL knockout mice and AAV6-WASL-mediated N-WASP expression confirmed that EcN-Sj16-Exo alleviates experimental asthma by upregulating N-WASP to inhibit EET formation.

Conclusion: Our findings suggest that EcN-Sj16-Exo represents a promising therapeutic approach in asthma, highlighting the potential of targeting EETs and N-WASP in asthma therapy.

背景:嗜酸性粒细胞炎症是过敏性哮喘的一个特征,嗜酸性粒细胞减少可缓解症状。支气管肺泡灌洗液(BALF)中嗜酸性粒细胞细胞外陷阱(EETs)水平升高与哮喘严重程度相关。Sj16是一种来自日本血吸虫的蛋白,具有已知的免疫调节特性。外泌体具有保护磷脂双分子层,是有效的药物载体。方法:通过大肠杆菌Nissle 1917提取表达Sj16 (EcN-Sj16-Exo)的外泌体,探讨EcN-Sj16-Exo在哮喘中的作用。在卵清蛋白(OVA)诱导的小鼠哮喘模型中,EET水平升高。用EcN-Sj16-Exo治疗实验性哮喘模型。用免疫荧光和扫描电镜观察EET的形成。评估肺功能、气道重塑和炎症。采用Wiskott-Aldrich综合征样(WASL)敲除小鼠和表达神经Wiskott-Aldrich综合征蛋白(N-WASP)的重组腺相关病毒(rAAV)研究EcN-Sj16-Exo的潜在机制。结果:哮喘患者痰液中EET的形成增加,半胱氨酸增多。我们证明Sj16在体外抑制EET的形成,并且当由EcN-Sj16分泌时,Sj16主要定位于外泌体。在实验性哮喘模型中,EcN-Sj16-Exo显著减少EET的形成。此外,EcN-Sj16-Exo显著减轻气道高反应性(AHR)和气道重塑,表现为肺阻力(RL)降低,动态顺应性(Cdyn)改善,炎症细胞浸润、纤维化和粘液分泌增多。此外,EcN-Sj16-Exo降低了BALF中的嗜酸性粒细胞和中性粒细胞计数、IgE和2型细胞因子水平,同时增加了脾脏中的Treg细胞。机制上,EcN-Sj16-Exo通过上调N-WASP抑制EET的形成。WASL敲除小鼠和aav6 -WASL介导的N-WASP表达证实,EcN-Sj16-Exo通过上调N-WASP抑制EET的形成来缓解实验性哮喘。结论:我们的研究结果表明,EcN-Sj16-Exo是一种很有前景的哮喘治疗方法,突出了靶向eet和N-WASP在哮喘治疗中的潜力。
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引用次数: 0
Persistent tachypnoea of infancy (PTI/NEHI) and obesity in SRRM2-related developmental disorder. 婴儿持续性呼吸急促(PTI/NEHI)与srrm2相关发育障碍中的肥胖
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.02135-2025
Christina K Rapp, Julia Rodler, Katharina Mauss-Schwarzer, Florian Gothe, Simone Reu-Hoefer, Dorit Aschmann-Mühlhans, Markus Egger, Ernst Eber, Freerk Prenzel, Matthias Griese
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引用次数: 0
Reply: Paediatric-onset bronchiectasis: an overlooked facet in the multifaceted approach to bronchiectasis. 回复:儿科发作的支气管扩张:支气管扩张的多方面入路中一个被忽视的方面。
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.01660-2025
Luai Khalaili, Stefano Aliberti, Francesco Blasi, James Chalmers, Michal Shteinberg
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引用次数: 0
An incomplete map: diagnostic gaps in bronchiectasis by age of onset. 一个不完整的地图:诊断差距在支气管扩张的年龄发作。
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.01578-2025
Yujiao Wu, Yaling Li, Jun Li
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引用次数: 0
Exciting times for trimodulin. 对于三调素来说,这是激动人心的时刻。
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.02297-2025
Rory E Morty
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引用次数: 0
Going deeper, reaching broader: proteomic ARDS phenotyping in East Asian critical care. 更深入,更广泛:东亚重症监护中的ARDS蛋白质组表型分析。
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.02254-2025
Nanditha Venkatesan, Georgios D Kitsios
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引用次数: 0
Reply to: An incomplete map: diagnostic gaps in bronchiectasis by age of onset. 回复:一个不完整的地图:支气管扩张的年龄诊断差距。
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.01810-2025
Michal Shteinberg, Luai Khalaili, Nili Stein, Stefano Aliberti, Francesco Blasi, James D Chalmers
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引用次数: 0
Inflammation and mucus properties in inherited diseases of mucociliary clearance. 粘膜纤毛清除遗传性疾病的炎症和粘液特性。
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.02426-2025
Amelia Shoemark
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引用次数: 0
Addressing the global challenges of COPD and asthma: a shared vision from the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) and the Global Initiative for Asthma (GINA). 应对COPD和哮喘的全球挑战:慢性阻塞性肺疾病全球倡议(GOLD)和哮喘全球倡议(GINA)的共同愿景
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.02244-2025
David M G Halpin, Refiloe Masekela, Claus F Vogelmeier, Obianuju B Ozoh, Alvaro A Cruz, Helen K Reddel, Arzu Yorgancioglu, Alvar Agusti
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引用次数: 0
SRRM2 and neuroendocrine cell hyperplasia of infancy: connecting neurodevelopment to the lungs. SRRM2与婴儿期神经内分泌细胞增生:连接神经发育与肺。
IF 21 1区 医学 Q1 RESPIRATORY SYSTEM Pub Date : 2026-02-05 Print Date: 2026-02-01 DOI: 10.1183/13993003.01869-2025
Silvestre Cuinat
{"title":"<i>SRRM2</i> and neuroendocrine cell hyperplasia of infancy: connecting neurodevelopment to the lungs.","authors":"Silvestre Cuinat","doi":"10.1183/13993003.01869-2025","DOIUrl":"10.1183/13993003.01869-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"67 2","pages":""},"PeriodicalIF":21.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
European Respiratory Journal
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