Pub Date : 2026-02-19DOI: 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.
{"title":"EcN-Sj16-Exo ameliorates experimental asthma by inhibiting eosinophil extracellular traps formation <i>via</i> N-WASP upregulation.","authors":"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","doi":"10.1183/13993003.00948-2025","DOIUrl":"https://doi.org/10.1183/13993003.00948-2025","url":null,"abstract":"<p><strong>Background: </strong>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 <i>Schistosoma japonicum</i> with known immunoregulatory properties. Exosomes, with their protective phospholipid bilayer, serve as efficient drug carriers.</p><p><strong>Methods: </strong>We extracted exosomes secreted by <i>Escherichia coli</i> 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 (<i>WASL</i>) 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.</p><p><strong>Results: </strong>EET formation was increased in sputum and BALF from asthma patients. We demonstrate that Sj16 inhibits EET formation <i>in vitro</i> 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 (R<sub>L</sub>), improved dynamic compliance (C<sub>dyn</sub>), 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. <i>WASL</i> 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225004","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 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
{"title":"Persistent tachypnoea of infancy (PTI/NEHI) and obesity in <i>SRRM2</i>-related developmental disorder.","authors":"Christina K Rapp, Julia Rodler, Katharina Mauss-Schwarzer, Florian Gothe, Simone Reu-Hoefer, Dorit Aschmann-Mühlhans, Markus Egger, Ernst Eber, Freerk Prenzel, Matthias Griese","doi":"10.1183/13993003.02135-2025","DOIUrl":"10.1183/13993003.02135-2025","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":"146124275","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 10.1183/13993003.01660-2025
Luai Khalaili, Stefano Aliberti, Francesco Blasi, James Chalmers, Michal Shteinberg
{"title":"Reply: Paediatric-onset bronchiectasis: an overlooked facet in the multifaceted approach to bronchiectasis.","authors":"Luai Khalaili, Stefano Aliberti, Francesco Blasi, James Chalmers, Michal Shteinberg","doi":"10.1183/13993003.01660-2025","DOIUrl":"10.1183/13993003.01660-2025","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":"146124323","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 10.1183/13993003.01578-2025
Yujiao Wu, Yaling Li, Jun Li
{"title":"An incomplete map: diagnostic gaps in bronchiectasis by age of onset.","authors":"Yujiao Wu, Yaling Li, Jun Li","doi":"10.1183/13993003.01578-2025","DOIUrl":"10.1183/13993003.01578-2025","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":"146124050","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 10.1183/13993003.02297-2025
Rory E Morty
{"title":"Exciting times for trimodulin.","authors":"Rory E Morty","doi":"10.1183/13993003.02297-2025","DOIUrl":"10.1183/13993003.02297-2025","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":"146124087","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 10.1183/13993003.02254-2025
Nanditha Venkatesan, Georgios D Kitsios
{"title":"Going deeper, reaching broader: proteomic ARDS phenotyping in East Asian critical care.","authors":"Nanditha Venkatesan, Georgios D Kitsios","doi":"10.1183/13993003.02254-2025","DOIUrl":"10.1183/13993003.02254-2025","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":"146124317","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 10.1183/13993003.01810-2025
Michal Shteinberg, Luai Khalaili, Nili Stein, Stefano Aliberti, Francesco Blasi, James D Chalmers
{"title":"Reply to: An incomplete map: diagnostic gaps in bronchiectasis by age of onset.","authors":"Michal Shteinberg, Luai Khalaili, Nili Stein, Stefano Aliberti, Francesco Blasi, James D Chalmers","doi":"10.1183/13993003.01810-2025","DOIUrl":"10.1183/13993003.01810-2025","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":"146124331","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 10.1183/13993003.02426-2025
Amelia Shoemark
{"title":"Inflammation and mucus properties in inherited diseases of mucociliary clearance.","authors":"Amelia Shoemark","doi":"10.1183/13993003.02426-2025","DOIUrl":"10.1183/13993003.02426-2025","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":"146124352","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 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
{"title":"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).","authors":"David M G Halpin, Refiloe Masekela, Claus F Vogelmeier, Obianuju B Ozoh, Alvaro A Cruz, Helen K Reddel, Arzu Yorgancioglu, Alvar Agusti","doi":"10.1183/13993003.02244-2025","DOIUrl":"10.1183/13993003.02244-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458203","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}
Pub Date : 2026-02-05Print Date: 2026-02-01DOI: 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}