American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"Gene-ius at Work: Decoding Cell States through Expression.","authors":"Soula Danopoulos, Denise Al Alam","doi":"10.1165/rcmb.2025-0168ED","DOIUrl":"10.1165/rcmb.2025-0168ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"485-486"},"PeriodicalIF":5.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957131","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":"Single-Cell RNA Sequencing Identifies a Unique Macrophage Population in a Mouse Model of Ozone-induced Asthma Exacerbation.","authors":"Jess L Ray, Joshua Walum, Daria Jelic, Ryelie Barnes, Ian D Bentley, Rodney D Britt, Joshua A Englert, Megan N Ballinger","doi":"10.1165/rcmb.2024-0358OC","DOIUrl":"10.1165/rcmb.2024-0358OC","url":null,"abstract":"<p><p>Ozone (O₃) inhalation triggers asthmatic airway hyperresponsiveness (AHR), but the mechanisms are unknown. Previously, we developed a murine model of dust mite, ragweed, and <i>Aspergillus</i> (DRA)-induced allergic lung inflammation followed by O₃ exposure for mechanistic investigation. The present study used single-cell RNA sequencing for unbiased profiling of cells within the lungs of mice exposed to DRA, O₃, or DRA + O₃ to identify components of the immune cell niche that contribute to AHR. Alveolar macrophages (AMs) had the greatest number of differentially expressed genes after DRA + O₃, most of which were unique to the two-hit exposure. After DRA + O₃, AMs activated transcriptional pathways related to cholesterol biosynthesis, degradation of the extracellular matrix, endosomal Toll-like receptor processing, and various cytokine signals. We also identified AM and monocyte subset populations that were unique to the DRA + O₃ group. These unique AMs activated gene pathways related to inflammation, sphingolipid metabolism, and bronchial constriction. The unique monocyte population had a gene signature that suggested phospholipase activation and increased degradation of the extracellular matrix. Flow cytometric analysis of BAL immune cells showed recruited monocyte-derived AMs after DRA and DRA + O₃, but not after O₃ exposure alone. O₃ alone increased BAL neutrophils, but this response was attenuated in DRA + O₃ mice. DRA-induced changes in the airspace immune cell profile were reflected in elevated BAL cytokine/chemokine levels after DRA + O₃ compared with O₃ alone. The present work highlights the role of monocytes and AMs in the response to O₃ and suggests that the presence of distinct subpopulations after allergic inflammation may contribute to O₃-induced AHR.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"586-599"},"PeriodicalIF":5.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661565","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":"Transcriptomic Profiling of Long COVID-19 in Patients with Interstitial Lung Disease Reveals Dysregulation of Mitochondrial Oxidative Phosphorylation.","authors":"Katherine A Aracena, Grace C Nwankwo, Cathryn T Lee, Rasika Karnik, Iazsmin Ventura, Dylan Douglas, Inem Udofia, Mengjie Chen, Lydia Chelala, Hae Kyung Im, Mary E Strek, Ayodeji Adegunsoye","doi":"10.1165/rcmb.2024-0595LE","DOIUrl":"10.1165/rcmb.2024-0595LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"634-637"},"PeriodicalIF":5.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959995","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":"Tartrate-Resistant Acid Phosphatase 5 (TRAP5) Promotes Eosinophil Migration During Allergic Asthma.","authors":"Médea Padra, Jesper Bergwik, Anna Adler, Genevieve Marcoux, Ravi K V Bhongir, Praveen Papareddy, Arne Egesten","doi":"10.1165/rcmb.2024-0304OC","DOIUrl":"10.1165/rcmb.2024-0304OC","url":null,"abstract":"<p><p>Allergic asthma is characterized by Type 2 inflammation and eosinophilia. Tartrate-resistant acid phosphatase 5 (TRAP5; also referred to as acid phosphatase 5 [ACP5]) is a metallophosphatase expressed by alveolar macrophages that dephosphorylates osteopontin, a phosphoglycoprotein with increased expression in asthma. To investigate the role of TRAP5 during asthma, we used a murine model of ovalbumin (OVA)-induced allergic airway inflammation as well as IL-33-induced airway inflammation, including <i>Trap</i>5^-/- and wild-type (WT) mice. Histological analyses of murine lung revealed that OVA-induced inflammation induced the formation of inflammatory lesions and increased mucus production in both WT and <i>Trap</i>5^-/- mice. However, lower cytokine levels (including IL-5 and IL-13) were detected by multiplex immunoassay in <i>Trap</i>5^-/- mice after OVA-induced inflammation. Furthermore, quantitative PCR analysis detected different gene expression profiles of <i>Trap</i>5^-/-/OVA mice, including upregulation of <i>Il-17a</i> and downregulation of <i>Il-33</i>. Lower eosinophil numbers were measured in BAL fluid of <i>Trap</i>5^-/-/OVA mice using flow cytometry analysis, whereas immunofluorescence staining revealed a high eosinophil number in lung tissue of both groups with OVA challenge. In the IL-33 model of Type 2 inflammation, both WT and <i>Trap</i>5^-/- mice showed similar inflammatory responses with regard to cytokine levels and cell recruitment patterns. <i>In vitro</i>, eosinophil chemotaxis was facilitated by nonphosphorylated, but not phosphorylated, osteopontin, an effect inhibited by an α4β1 integrin inhibitor. The results suggest that TRAP5 is important in the recruitment of immune cells, including eosinophils, as well as in shaping the profile and amplification of the inflammatory response during allergic airway inflammation. Thus, TRAP5 may serve as a therapeutic target in allergic asthma.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"612-622"},"PeriodicalIF":5.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770942","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":"A Human Single-Nuclei Atlas Reveals Novel Cell States during the Pseudoglandular-to-Canalicular Transition.","authors":"Laurent Renesme, Flore Lesage, David P Cook, Adithya Achuthan, Shumei Zhong, Satu M Hänninen, Olli Carpén, Ivana Mižik, Bernard Thébaud","doi":"10.1165/rcmb.2024-0244OC","DOIUrl":"10.1165/rcmb.2024-0244OC","url":null,"abstract":"<p><p>Most of our knowledge of human lung development is derived from morphologic studies and extrapolations of the underlying molecular mechanisms from animal models. Here we describe developmental changes in human fetal lungs during the pseudoglandular and early canalicular period, detailing this critical but previously poorly described transition period. We report the cellular composition and cell-to-cell communication in a single-nuclei dataset from nine human fetal lungs between 14 and 19 weeks of gestation. We identified 9 main populations and 19 subpopulations, including the rare pulmonary neuroendocrine cells. For each population, marker genes were reported, and selected markers were validated. Enrichment analysis were performed to explore the potential molecular mechanisms and pathways within individual populations according to gestational age. Finally, cell-to-cell communication was studied using ligand-receptor analysis among the different cell types. General developmental pathways, as well as pathways involved in vasculogenesis, neurogenesis, and immune regulation, were identified. This study provides an important background to generate research hypotheses in projects studying normal or impaired lung development and help to validate surrogate models (e.g., lung organoids) to study human lung development.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"500-516"},"PeriodicalIF":5.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810233","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":"eNAMPT Is a Novel DAMP and Therapeutic Target in Human and Murine Pulmonary Fibrosis.","authors":"Nancy G Casanova, Jose D Herazo-Maya, Carrie L Kempf, Belinda L Sun, Jin H Song, Annie Hernandez, Jason Canizales Galaviz, Xiaoguang Sun, Sara M Camp, Julie G Ledford, Riley D Hellinger, Marisela Rodriguez, Amy Y Zhao, Avraham Unterman, Ivan Rosas, Steve Duncan, Victor J Thannikal, Matthew K Hufford, Mohamed Ahmed, Nahla Zaghloul, Akash Gupta, Christian Bime, Saad Sammani, Ben N Stansfield, Jinjing Chen, Annadurai Anandhan, Matthew D Disney, Aikseng Ooi, Shaira L Kee, Theodoros Karampitsakos, Panayiotis V Benos, Naftali Kaminski, Donna Zhang, Joe G N Garcia","doi":"10.1165/rcmb.2024-0342OC","DOIUrl":"10.1165/rcmb.2024-0342OC","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disorder without curative therapies, underscoring the critical unmet need for identification of novel therapeutic strategies. eNAMPT (extracellular nicotinamide phosphoribosyltransferase) is a damage-associated molecular pattern protein (DAMP) and TLR4 (Toll-like receptor 4) ligand that contributes to the severity of radiation-induced lung fibrosis and nonalcoholic steatohepatitis-associated hepatic fibrosis. This study investigates eNAMPT as a druggable target in human and preclinical IPF using the eNAMPT-neutralizing ALT-100 monoclonal antibody (mAb). Blood, peripheral blood mononuclear cells (PBMCs), and lung tissues from patients with IPF and from an experimental bleomycin-induced lung fibrosis model in C57Bl6 mice were analyzed. Biochemical and histologic measurements, as well as gene expression through bulk and single-cell RNA sequencing of human PBMCs and murine lung tissues, were performed. Human studies revealed NAMPT expression to be significantly increased in plasma, lung tissues, and PBMCs from subjects with IPF, correlating with disease severity and inversely associated with IPF survival. Bleomycin-exposed mice exhibited increased inflammatory indices associated with lung fibrosis development (including NAMPT levels), as well as physiologic lung stiffening and TGF-β pathway-related protein and gene expression, with each index significantly mitigated in mice receiving ALT-100 mAb. Single-cell RNA sequencing studies demonstrated the ALT-100 mAb to reverse the bleomycin-induced dramatic expansion of alveolar type 2 epithelium and induction of endothelial cell- and epithelial cell-to-mesenchymal/myofibroblast transitions. These finding support the fundamental involvement of eNAMPT/TLR4 signaling pathway in lung fibrosis pathobiology, with eNAMPT neutralization a viable therapeutic strategy to directly address the unmet need for novel IPF treatments.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"572-585"},"PeriodicalIF":5.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690902","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":"Thymic Stromal Lymphopoietin Promotes Ozone-induced Inflammation in the Airway.","authors":"Hiroki Tashiro, Yuki Kurihara, Yuki Kuwahara, Yoshie Konomi, Masato Asaoka, Hiroki Kabata, Koichi Fukunaga, Ayako Takamori, Toshihiro Morisaki, Shinya Kimura, Naoko Sueoka-Aragane, Koichiro Takahashi","doi":"10.1165/rcmb.2025-0281OC","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0281OC","url":null,"abstract":"<p><p>Ozone is associated with induction of airway hyperresponsiveness (AHR) and neutrophilic airway inflammation which is the characteristic of type 2 low inflammatory phenotype. Recently, epithelial cell-derived cytokines such as thymic stromal lymphopoietin (TSLP) have been recognized as therapeutic targets for asthma with type 2 low inflammation, but the mechanisms remain unknown. In the present study, BALB/c mice and TSLP receptor-deficient mice were exposed to ozone at 2 ppm for 3 hours. AHR, cell counts, and cytokine analyses of bronchoalveolar lavage fluid (BALF) were examined. Single-cell RNA sequencing was performed to explore targeted cell clusters and genes. <i>Batf3</i>-deficient mice were analyzed to assess the effects of conventional type 1 dendritic cells (cDC1s), and treatment with NP-G2-044 was given to evaluate the impact of <i>Fscn1</i> on ozone-induced airway responses. Ozone-exposed BALB/c mice showed greater AHR and neutrophils in BALF, with higher levels of TSLP in lungs than air-exposed BALB/c mice. Ozone-exposed TSLP receptor-deficient mice showed lower AHR and neutrophil counts in BALF than BALB/c mice. Single-cell RNA sequencing showed that DCs, especially cDC1s, were modified by ozone exposure and blockade of TSLP in terms of gene expressions including <i>Fscn1</i>. Ozone-exposed <i>Batf3</i>-deficient mice showed lower AHR and neutrophil counts in BALF, with depletion of cDC1s compared with C57BL/6J mice. Expression of <i>Fscn1</i> was greater in bone marrow-derived cDC1s stimulated by TSLP, and ozone-exposed BALB/c mice treated with NP-G2-044 showed lower neutrophils in BALF than BALB/c mice treated with placebo. For conclusion, cDC1 derived <i>Fscn1</i> was a potential target for ozone-induced neutrophilic airway inflammation via TSLP.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197916","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":"Functional Variant Discovery Identifies a Novel Genetic Link Between <i>SPRY2</i>, Wood Smoke, and Asthma.","authors":"Arnav Gupta, Amber Dahlin, Alejandra Macario, Fabienne Gally, Michael R Weaver, Samuel Guarino, Louisa Kahn, Lynn Sanford, Margaret A Gruca, Michael H Cho, Robin D Dowell, Scott T Weiss, Sarah K Sasse, Anthony N Gerber","doi":"10.1165/rcmb.2024-0587OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0587OC","url":null,"abstract":"<p><p>As a consequence of climate change and land use policies, there has been a historic rise in wildfire smoke across the United States and the world. While the deleterious effects of wildfire smoke and associated air pollution on asthma outcomes are established epidemiologically, genetic risks and molecular mechanisms of how wildfire smoke affects asthma are unknown. This knowledge gap hinders the identification of high-risk individuals and the creation of targeted therapies or recommendations to protect these individuals. We identified 52 genetic risk variants that colocalized with genomic responses to wood smoke particles (WSP), a model of wildfire particulate matter, and associated with asthma in the Genetic Epidemiology Research on Aging (GERA) cohort. We used additional filters to prioritize variants for direct testing of allele-dependent transcriptional regulatory function in plasmid reporters. We found that the rs3861144 variant (Odds Ratio_asthma = 1.036) changes <i>SPRY2</i> responses to WSP in airway epithelial cells, which are involved in Interleukin-8 secretion, Extracellular Signal-related Kinase (ERK) activation, and mechanical scratch repair in cell culture. These findings provide insights into the molecular pathways through which WSP may influence asthma risk and propose genetic candidates that warrant further study for their potential as clinical tools for asthma.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184585","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":"Homing Instincts: Systemic Cell-delivery for Lung Disease.","authors":"Finn J Hawkins","doi":"10.1165/rcmb.2025-0415ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0415ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147383","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":"From Splicing Landscape to Therapeutic Targets: Long-Read Sequencing in Non-Small-Cell Lung Cancer.","authors":"Wei Chen, Pedro L Baldoni, Anny Xiaobo Zhou","doi":"10.1165/rcmb.2025-0483ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0483ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147349","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}