American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"Siglec-F Deficiency Prevents Fibrosis after Bleomycin-induced Acute Lung Injury.","authors":"Marika Orlov, Naoko Hara, Sunad Rangarajan, Ana M Jaramillo, Qihua Ye, Yuliana M Romo-Perez, Kenny Ngo, James C NeeDell, Anna Q Harder, Fan Jia, Brian Vestal, Rachel Z Blumhagen, Ting Hui Tu, Jazalle McClendon, Alexandra L McCubbrey, Bradford J Smith, David A Schwartz, William J Janssen, Christopher M Evans","doi":"10.1165/rcmb.2024-0402LE","DOIUrl":"10.1165/rcmb.2024-0402LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Von Willebrand Factor: An Unhealthy Bond Between Lung Endothelium and Pulmonary Fibrosis.","authors":"Jie Chao, Laszlo Farkas","doi":"10.1165/rcmb.2025-0300ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0300ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hermansky-Pudlak Syndrome Pulmonary Fibrosis: Monogenic Disorder, Multi-omics Discovery.","authors":"Alexander Ghincea, Erica L Herzog","doi":"10.1165/rcmb.2025-0410ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0410ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Don't Stress: We're One Step Closer to Host-Directed Therapy for Influenza.","authors":"Jaime L Hook","doi":"10.1165/rcmb.2025-0416ED","DOIUrl":"10.1165/rcmb.2025-0416ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12349310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-tuning ILC2s: CD48 Pumps Up the Volume.","authors":"Yung-An Huang, Taylor A Doherty","doi":"10.1165/rcmb.2025-0381ED","DOIUrl":"10.1165/rcmb.2025-0381ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choline and CCL22 Are Prognostic Blood Biomarkers for Hermansky-Pudlak Syndrome Pulmonary Fibrosis.","authors":"Muhammad Arif, Abhishek Basu, Ben Long G Zuo, Mei Xing G Zuo, Kevin J O'Brien, Lenny Pommerolle, Lourdes M Caro-Rivera, Wilfredo De Jesus-Rojas, Marcos J Ramos-Benitez, Molly Behan, Wendy J Introne, Graeme Frost, Ruin Moaddel, William A Gahl, May Christine V Malicdan, Bernadette R Gochuico, Resat Cinar","doi":"10.1165/rcmb.2024-0628OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0628OC","url":null,"abstract":"<p><p>Identifying molecular biomarkers of pulmonary fibrosis (PF) would improve monitoring the disease progression and response to treatment. Hermansky-Pudlak syndrome (HPS) PF is an inherited type of progressive PF with accelerated onset of PF in patients with HPS type 1 (HPS-1). HPSPF could serve as a model to study biomarkers of progressive PF, given that all HPS-1 subjects eventually develop HPSPF. We utilized a multi-omics strategy to discover progressive blood biomarkers that can recognize factors contributing to the fibrotic cascade in the lungs of HPS subjects. Metabolomic and cytokine/chemokine profiling were performed on serum samples from patients with HPS-1, HPS-1 with PF (HPSPF), HPS-3 or HPS-5, idiopathic PF (IPF), and normal volunteers. Metabolomics, cytokine/chemokine, pulmonary function, and age data from HPS-1 and HPSPF subjects were integrated into a multi-omics network. The analysis highlighted alterations in the transsulfuration pathway, arginine metabolism, and redox balance with the progression of PF in HPS-1. Among those, CCL22 and choline were significantly elevated in HPSPF compared to HPS-1 in two independent cohorts together with age and associated with decline of pulmonary function. In ROC curve analysis, both CCL22 and choline demonstrated high accuracy in predicting PF in HPS-1 subjects, could serve as prognostic blood biomarkers of HPSPF. We noted similarity in molecular signatures of CCL22 in progressive IPF and HPSPF. We found that inducible nitric oxide synthase (iNOS) is an upstream regulator of releasing profibrotic mediators (CCL22, CCL24, IL-18, IL1α, IL1β), suggesting therapeutic potential of iNOS inhibition in progressive HPSPF.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ER Stress Disrupts the Airway Epithelium and Reduces Host Defense during Influenza A Virus Infection.","authors":"Erin Y Earnhardt, Jennifer L Tipper, Mohamed A Hanafy, Ahmed Lazrak, Abel Lopez, Sarah E Perritt, David C LaFon, James A Mobley, George M Solomon, Kevin S Harrod","doi":"10.1165/rcmb.2025-0141OC","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0141OC","url":null,"abstract":"<p><p>Secondary <i>Streptococcus pneumoniae (Spn)</i> infection to influenza A virus (IAV) frequently leads to an increase in morbidity and mortality of IAV. Our recent work establishes that IAV infection disrupts bacterial host defense in the lung epithelium through loss of cystic fibrosis transmembrane conductance regulator protein (CFTR) function, causing an acidification of the ASL and subsequently increasing susceptibility to <i>Spn</i>. Infection with IAV and other respiratory pathogens cause a robust endoplasmic reticulum (ER) stress response. However, the role of this acute ER stress response in predisposing the airway epithelium to susceptibility to bacterial infections remains unknown. Utilizing a primary differentiated human bronchial airway epithelial cell (HBEC) culture system, we find that both IAV-induced ER stress and ER stress alone increase susceptibility to <i>Spn</i> in the airway epithelium and lead to a loss of CFTR activity, subsequently causing a disruption in the rheostatic properties of the airway surface liquid. Importantly, in HBECs without functional CFTR, modulation of ER stress in the presence and absence IAV of has no effect on susceptibility to <i>Spn</i>. Restoration of ASL pH after ER stress in HBECs with functional CFTR reduces <i>Spn</i>, suggesting that ER stress increases susceptibility to bacterial infection by disrupting CFTR and causing an acidification of the ASL. Here, we demonstrate a clear role for ER stress in disruption of both the airway epithelium and bacterial host defense mechanisms during respiratory viral infection.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CD48 Ameliorates ILC2-mediated Airway Hyperreactivity by Disrupting the PKCβ Pathway.","authors":"Kei Sakano, Yoshihiro Sakano, Benjamin P Hurrell, Mohammad H Kazemi, Xin Li, Stephen Shen, Omid Akbari","doi":"10.1165/rcmb.2025-0299OC","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0299OC","url":null,"abstract":"<p><p>CD48 is a cell surface protein belonging to the signaling lymphocyte activation molecule family and is known to regulate immune cell function. Although asthma has traditionally been associated with adaptive immune responses, recent evidence highlights a central role for group 2 innate lymphoid cells (ILC2s) in orchestrating type 2 inflammation, independent of adaptive immunity. Here, we investigated the immunomodulatory function of CD48 on ILC2s and its contribution to the development of airway inflammation and airway hyperreactivity (AHR). Using an ILC2 dependent induced murine model of asthma, we employed both CD48 knockout mice and blocking antibodies to dissect the role of CD48 in vivo. We found that CD48 is expressed on lung-resident ILC2s, and its absence significantly impairs ILC2 activation, reduces eosinophilic infiltration, and alleviates AHR. Adoptive transfer experiments further confirmed that these effects are ILC2-intrinsic. Transcriptomic profiling of CD48-deficient ILC2s revealed downregulation of key effector genes and enrichment of pathways involving PI3K and protein kinase C beta (PKCβ). Pharmacologic modulation of PKCβ altered ILC2 cytokine production in a CD48-dependent manner, establishing a mechanistic link between CD48 signaling and ILC2 function. Moreover, human ILC2s isolated from peripheral blood and cultured under activating conditions upregulated CD48, and blockade of CD48 suppressed ILC2s cytokine production. In a humanized mouse model, CD48 inhibition likewise reduced airway inflammation, mirroring findings in murine systems. These results identify CD48 as a critical regulator of ILC2-driven AHR and suggest that targeting CD48 or its downstream signaling pathways may offer novel therapeutic opportunities for the treatment of asthma.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyaluronan Ameliorates Viral Pneumonia in Mice and Humans by Inhibiting E2F1 Transcription Factor.","authors":"Vandy P Stober, Carol S Trempus, Flavia Galdi, Negin P Martin, Wesley Gladwell, Michael Cronce, Jeffery S Cox, Jay D Keasling, Jonathan Budzik, Shih-Heng Chen, Yosuke Sakamachi, Jian-Liang Li, Christopher A McGee, Daniel J Zaccaro, Jane S Der, Charles J Tucker, Erica Scappini, Javier Campos Gomez, Steven M Rowe, Mary K Cowman, Christina M Barkauskas, Patty J Lee, Matthew R Markovetz, Brian Button, David B Hill, Dorothea A Erxleben, Adam R Hall, Jian Liu, Yongmei Xu, Claudio Pedone, Raffaele Antonelli-Incalzi, Sadis Matalon, Rashmin C Savani, Stavros Garantziotis","doi":"10.1165/rcmb.2025-0173OC","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0173OC","url":null,"abstract":"<p><strong>Rationale: </strong>Viral lung infections are a major cause of morbidity and mortality worldwide. Despite significant advances in vaccines and antivirals, there remains a tremendous need for broadly applicable treatments that can be utilized across viral infections. Prior to infecting epithelial cells, viruses interact with the epithelial glycocalyx, which contains high molecular weight hyaluronan (HMWHA), a glycosaminoglycan that has beneficial effects in lung injury.</p><p><strong>Objective: </strong>To determine the role of HMWHA in viral pneumonia.</p><p><strong>Methods: </strong>We infected mice with Influenza or SARS-Cov2 and treated with prophylactic or therapeutic doses of HMWHA or saline control. We performed in vitro experiments of infection with viruses of respiratory and non-respiratory human and animal cells and evaluated the effect of HMWHA on infection. We analyzed existing databases for expression of hyaluronan and the transcription factor E2F1. Finally, we performed a clinical trial with HMWHA in patients with severe COVID-19 Measurements and Main Results: Exogenously applied HMWHA improved survival in SARS-CoV2 and influenza infection in mice, by ameliorating inflammation via the inhibition of E2F1. In a clinical study, inhaled HMWHA improved outcomes in patients with severe COVID-19. Furthermore, airway epithelia naturally express HMWHA, which is induced during viral infection and prevents infection via macromolecular crowding of viruses.</p><p><strong>Conclusions: </strong>Our data provide a mechanistic justification for the use of HMWHA as a broadly effective prophylactic and therapeutic agent in viral airway infection. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VWF Deficiency Inhibits EndoMT to Attenuate Pulmonary Fibrosis.","authors":"Wenjie Wang, Shiyi Chen, Zhuyi Xi, Yuan Si, Yi Liu, Jing Chen, Bingshun Wang, Di Zhu, Likun Gong","doi":"10.1165/rcmb.2024-0527OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0527OC","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, interstitial lung disease lacking efficient drug to reverse it. Thus, to elucidate the complex pathogenesis of IPF and identify new therapeutic targets are urgently needed. It has been revealed that the pathophysiology of IPF is a highly orchestrated process including multiple cell types, where the contribution of endothelial cells (ECs) has also been attracted researchers' attention. However, although the involvement of ECs in fibrosis has been recognized, the underlying key molecules driving these changes are not well-defined. Here, we revealed that von Willebrand factor (VWF), a marker of damaged ECs, and endothelial dysfunction are positively correlated with IPF progression based on reanalysis of gene expression profiles of patients with IPF. Next, we discovered that <i>VWF</i> deficiency attenuated fibrosis in experimental models, including human cell lines (<i>in vitro</i>) and mice (<i>in vivo</i>). Mechanistically, <i>VWF</i> deficiency inhibited endothelial-to-mesenchymal transition (EndoMT), regulated vascular abnormalities and limited M2 macrophage infiltration, which were achieved, at least in part, by the inhibition of Wnt signaling. Our findings provided evidence for the pivotal role of ECs in IPF and revealed VWF might be a driving factor of EndoMT, suggesting that VWF can develop as a potential therapeutic target against IPF. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}