Dimitrios Toumpanakis, Vyronia Vassilakopoulou, Wen Gu, Eleftheria Mizi, Athanasia Chatzianastasiou, Vincent Richard, Christoph H Borchers, Yassene Mohammed, Carine Fillebeen, Theodoros Vassilakopoulos, Kostas Pantopoulos
{"title":"Iron Regulatory Protein 2 Deficiency Is Protective Against Resistive Breathing-induced Pulmonary Inflammation.","authors":"Dimitrios Toumpanakis, Vyronia Vassilakopoulou, Wen Gu, Eleftheria Mizi, Athanasia Chatzianastasiou, Vincent Richard, Christoph H Borchers, Yassene Mohammed, Carine Fillebeen, Theodoros Vassilakopoulos, Kostas Pantopoulos","doi":"10.1165/rcmb.2024-0286OC","DOIUrl":"10.1165/rcmb.2024-0286OC","url":null,"abstract":"<p><p>IRP2 (iron regulatory protein 2), a post-transcriptional regulator of cellular iron metabolism, has been associated with susceptibility to chronic obstructive pulmonary disease. Resistive breathing (RB) is the hallmark of the pathophysiology of obstructive airway diseases, especially during exacerbations, when increased mechanical stress is imposed on the lung. We have previously shown that RB, through tracheal banding, mimicking severe airway obstruction, induces pulmonary inflammation and injury in previously healthy mice. To characterize the role of IRP2 in RB-induced lung injury, wild-type and <i>Irp2<sup>-/-</sup></i> mice were subjected to tracheal banding surgery. RB increased tissue elasticity and viscance in wild-type but not in <i>Irp2<sup>-/-</sup></i> mice, denoting that the latter were protected against lung injury. Moreover, <i>Irp2<sup>-/-</sup></i> mice exhibited a lower score of lung inflammation. In addition, only wild-type but not <i>Irp2<sup>-/-</sup></i> mice responded to RB by increasing BAL cellularity due to higher macrophage count, which was accompanied by elevated BAL IL-1β and IL-6 concentrations. Lung proteomics and functional enrichment analysis revealed significant differences among wild-type and <i>Irp2<sup>-/-</sup></i> mice in RB-induced regulation of proteins involved in inflammatory and defense response pathways but also of many proteins with unknown function. We conclude that IRP2 supports proinflammatory activities in the lungs, whereas its deficiency protects against RB-induced pulmonary inflammation via remodeling of the lung proteome.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"73 1","pages":"96-108"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526114","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":"Erratum: Novel Porcine Model Reveals Two Distinct LGR5 Cell Types during Lung Development and Homeostasis.","authors":"","doi":"10.1165/rcmb.731Erratum","DOIUrl":"10.1165/rcmb.731Erratum","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"73 1","pages":"156"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537776","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}
Olga Tura-Ceide, Julia Oto, Jeisson Osorio, David Hervás, Víctor I Peinado, Verónica Sánchez-López, Elena Arellano, Miquel Gratacós, Cristina Bonjoch, Yolanda Torralba, Isabel Blanco, Pilar Medina, Remedios Otero, Joan Albert Barberà
{"title":"The Potential of Extracellular Microvesicle MicroRNAs in Precapillary Pulmonary Hypertension.","authors":"Olga Tura-Ceide, Julia Oto, Jeisson Osorio, David Hervás, Víctor I Peinado, Verónica Sánchez-López, Elena Arellano, Miquel Gratacós, Cristina Bonjoch, Yolanda Torralba, Isabel Blanco, Pilar Medina, Remedios Otero, Joan Albert Barberà","doi":"10.1165/rcmb.2024-0282LE","DOIUrl":"10.1165/rcmb.2024-0282LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"147-151"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555586","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":"Circulating Back to Blood: Erythrocyte Precursors Put the Brakes on Acute Lung Injury.","authors":"Jourdan E Brune, Anne M Manicone","doi":"10.1165/rcmb.2024-0632ED","DOIUrl":"10.1165/rcmb.2024-0632ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"14-15"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027823","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}
Nishanth R Shankar, Lorena Garnica, Emily Stahlschmidt, Andrew E Gelman, Derek Byers, Hrishikesh Kulkarni
{"title":"Characteristics of Human Donor Lungs Used for Research.","authors":"Nishanth R Shankar, Lorena Garnica, Emily Stahlschmidt, Andrew E Gelman, Derek Byers, Hrishikesh Kulkarni","doi":"10.1165/rcmb.2024-0442LE","DOIUrl":"10.1165/rcmb.2024-0442LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"151-155"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963528","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":"Loss of Iron Regulatory Protein 2 Protects Mice from Lung Inflammation during Bronchoconstriction.","authors":"Patricia P Ogger","doi":"10.1165/rcmb.2024-0638ED","DOIUrl":"10.1165/rcmb.2024-0638ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"12-13"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027825","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}
Ian Lee, Ananthakrishnan Ganesan, Laurynas Kalesinskas, Hong Zheng, Haejun C Ahn, Stephanie Christenson, Serpil C Erzurum, Joe Zein, Eugene R Bleecker, Deborah A Meyers, Mario Castro, John V Fahy, Elliot Israel, Nizar N Jarjour, Wendy C Moore, Sally E Wenzel, David T Mauger, Bruce D Levy, Prescott G Woodruff, Victor E Ortega, Purvesh Khatri
{"title":"Multicohort Analysis of Bronchial Epithelial Cell Expression in Healthy Subjects and Patients with Asthma Reveals Four Clinically Distinct Clusters.","authors":"Ian Lee, Ananthakrishnan Ganesan, Laurynas Kalesinskas, Hong Zheng, Haejun C Ahn, Stephanie Christenson, Serpil C Erzurum, Joe Zein, Eugene R Bleecker, Deborah A Meyers, Mario Castro, John V Fahy, Elliot Israel, Nizar N Jarjour, Wendy C Moore, Sally E Wenzel, David T Mauger, Bruce D Levy, Prescott G Woodruff, Victor E Ortega, Purvesh Khatri","doi":"10.1165/rcmb.2024-0125OC","DOIUrl":"10.1165/rcmb.2024-0125OC","url":null,"abstract":"<p><p>Asthma is a heterogeneous disease with variable presentation and characteristics. There is a critical need to identify underlying molecular endotypes of asthma. We performed the largest transcriptomic analysis of 808 bronchial epithelial cell samples across 11 independent cohorts, including 3 cohorts from the Severe Asthma Research Program. Using seven datasets (218 patients with asthma, 148 healthy control subjects) as discovery cohorts, we identified 505 differentially expressed genes, which we validated in the remaining four datasets. Unsupervised clustering using the 505 differentially expressed genes identified four reproducible clusters of patients with asthma across all datasets, corresponding to healthy control subjects, patients with mild/moderate asthma, and patients with severe asthma with significant differences in several clinical markers of severity, including pulmonary function, Type 2 inflammation, fractional exhaled nitric oxide, and maximum bronchodilator reversibility. Importantly, we found the same clusters in pediatric patients using nasal lavage fluid cells, demonstrating the gene signature and clusters are not confounded by age and are conserved in both lower and upper airways. The four asthma clusters may represent a unifying framework for understanding the molecular heterogeneity of asthma. Further study could potentially enable a precision medicine approach of matching therapies with patients with asthma most likely to benefit.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"73-87"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863023","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}
Pierre Janssen, Joan Abinet, Latifa Karim, Wouter Coppieters, Catherine Moermans, Julien Guiot, Florence Schleich, Coraline Radermecker, Thomas Marichal
{"title":"Comparison of Droplet- and Microwell-based Methods to Analyze Cryopreserved Human BAL Cells by Single-Cell RNA Sequencing.","authors":"Pierre Janssen, Joan Abinet, Latifa Karim, Wouter Coppieters, Catherine Moermans, Julien Guiot, Florence Schleich, Coraline Radermecker, Thomas Marichal","doi":"10.1165/rcmb.2024-0467MA","DOIUrl":"10.1165/rcmb.2024-0467MA","url":null,"abstract":"<p><p>Single-cell and single-nucleus RNA sequencing (scRNA-seq) has revolutionized the exploration of tissue biology and cellular heterogeneity by delivering transcriptomic data at the individual-cell level. However, the logistical challenge of utilizing fresh material has hindered investigations, particularly on human samples. Here, we aimed to address this limitation by implementing and comparing two cryopreservation and scRNA-seq methods for human BAL fluid (BALF) cells on the basis of droplet and microwell entrapment. Four BALF samples were collected from routine diagnostic procedures, and each sample was divided and processed using both techniques. Although the droplet-based method initially required a greater number of cells for fixation and cryopreservation, cells recovered postsequencing, and quality filtering displayed significantly higher counts of transcripts and genes per cell. This was particularly evident for alveolar macrophages, epithelial cells, mast cells, and T cells, whereas both methodologies were similarly able to capture transcripts from neutrophils. Of note, the microwell-based approach uniquely identified fragile eosinophils. We performed single-cell regulatory network inference and clustering analyses and found that the ability to predict the activities of key transcription factors implicated in the differentiation and identity of BALF immune cell populations correlated with the amounts of transcripts and genes per cell. Our results can serve as a resource for the design of large-scale translational and clinical projects involving scRNA-seq analyses.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"16-25"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109389","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}
Qiao Zhou, Yu-Long Yang, Jia-Feng Wang, Yu-Chao Dong, Jin Hou, Meng Guo, Wei Zhang, Yan-Fang Liu, Chong Bai
{"title":"Inflammation-induced Generation of Splenic Erythroblast-like Ter-Cells Inhibits the Progression of Acute Lung Injury via Artemin.","authors":"Qiao Zhou, Yu-Long Yang, Jia-Feng Wang, Yu-Chao Dong, Jin Hou, Meng Guo, Wei Zhang, Yan-Fang Liu, Chong Bai","doi":"10.1165/rcmb.2024-0407OC","DOIUrl":"10.1165/rcmb.2024-0407OC","url":null,"abstract":"<p><p>Identifying inflammation-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Nevertheless, how primary inflammation-induced nonleukocyte populations in distal organs contribute to ALI/ARDS remains poorly defined. Here, we report one population of erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119<sup>+</sup>CD45<sup>-</sup>CD71<sup>+</sup> phenotype in ALI/ARDS. Ter-cells induced by the spleen are chemoattracted into the lung to inhibit the progression of ALI by secreting the neurotrophic factor artemin into the blood and BAL fluid. <i>In vivo</i> blockade of Ter-cell-derived artemin aggravates lung injury, and artemin deficiency abolishes Ter-cells' antiinflammatory ability. We confirm the presence of circulating artemin in patients with ARDS and show that significantly elevated artemin correlates with good prognosis. We propose that Ter-cells and the secreted artemin play important roles in ALI/ARDS, with prognostic and therapeutic implications.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"73 1","pages":"37-48"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526113","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":"Surfactant Protein (SP)-A Benefits Over SP-A Mutant: A Preliminary Study for ILD Treatment.","authors":"Tifenn Desroziers, Yohan Soreze, Marie Legendre, Florence Dastot Le Moal, Valérie Nau, Serge Amselem, Irina Giurgea, Sonia Karabina, Camille Louvrier, Nadia Nathan","doi":"10.1165/rcmb.2024-0546OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0546OC","url":null,"abstract":"<p><p>Surfactant protein (SP)-A, an octadecamer composed of SP-A1 and SP-A2 is secreted into the alveolar space. Heterozygous variations in <i>SFTPA1</i> and <i>SFTPA2</i>, reported to impair protein secretion, have been associated with interstitial lung disease (ILD) and lung adenocarcinoma. To date, no specific treatment is available. Here, the impact of wild type (WT) SP-A1 or SP-A2 on the localization, oligomerization, and secretion of deleterious SP-A1 or SP-A2 variants is investigated. To achieve this, we used expression vectors carrying 4 previously described variations as well as a newly identified variation, in <i>SFTPA1</i> and <i>SFTPA2</i> or WT sequences. Proteins were transiently expressed in HEK293T, and after extraction, SP-A1 and SP-A2 were analyzed by Western blot to assess their stability, ability to form oligomers and secretion. Additionally, the subcellular localization of these proteins in HEK293 cells was examined using immunofluorescence microscopy. Consistent with previous reports, we observed that all the variations impair SP-A1 or SP-A2 secretion. Localization of mutated proteins was also disrupted. Furthermore, all variations in <i>SFTPA1</i> and <i>SFTPA2</i> exhibited defects in oligomerization of mutated proteins, along with lower expression levels. Interestingly, co-expression of SP-A1 or SP-A2 WT resulted in an increased expression of the mutated proteins, restored a proper oligomerization profile, and partially restored SP-A secretion. This study reveals the beneficial effect of SP-A WT on oligomerization and secretion of mutant SP-A suggesting that SP-A may be studied as a potential targeted treatment in ILD linked to SP-A molecular variations.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537774","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}