Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma
Abstract Mepolizumab (anti-IL5 therapy) reduces asthma exacerbations in urban children with exacerbation-prone eosinophilic asthma. We previously utilized nasal transcriptomics to identify inflammatory pathways (gene co-expression modules) associated with asthma exacerbations despite this therapy. I...
| 出版年: | Nature Communications |
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| 主要な著者: | , , , , , , , , , , , , , , , , , , , , |
| フォーマット: | 論文 |
| 言語: | 英語 |
| 出版事項: |
Nature Portfolio
2025-09-01
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| オンライン･アクセス: | https://doi.org/10.1038/s41467-025-63629-2 |
| _version_ | 1849290474682056704 |
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| author | Courtney L. Gaberino R. Max Segnitz Kimberly A. Dill-McFarland Leonard B. Bacharier Agustin Calatroni Michelle A. Gill Jeffrey Stokes Andrew H. Liu Robyn T. Cohen Rajesh Kumar Abigail Lang Gurjit K. Khurana Hershey Michael G. Sherenian Edward M. Zoratti Stephen J. Teach Meyer Kattan Patrice M. Becker Alkis Togias William W. Busse Daniel J. Jackson Matthew C. Altman |
| author_facet | Courtney L. Gaberino R. Max Segnitz Kimberly A. Dill-McFarland Leonard B. Bacharier Agustin Calatroni Michelle A. Gill Jeffrey Stokes Andrew H. Liu Robyn T. Cohen Rajesh Kumar Abigail Lang Gurjit K. Khurana Hershey Michael G. Sherenian Edward M. Zoratti Stephen J. Teach Meyer Kattan Patrice M. Becker Alkis Togias William W. Busse Daniel J. Jackson Matthew C. Altman |
| author_sort | Courtney L. Gaberino |
| collection | DOAJ |
| container_title | Nature Communications |
| description | Abstract Mepolizumab (anti-IL5 therapy) reduces asthma exacerbations in urban children with exacerbation-prone eosinophilic asthma. We previously utilized nasal transcriptomics to identify inflammatory pathways (gene co-expression modules) associated with asthma exacerbations despite this therapy. In this study, we applied differential gene correlation analysis on these targeted gene co-expression modules to gain better insight into the treatment effects on correlation structure within gene networks. Mepolizumab treatment resulted in loss of correlation amongst eosinophil-specific genes but conservation and even strengthening of correlation amongst mast cell-specific genes, T2 cytokines, and airway epithelial inflammatory genes. Notably, mepolizumab induced significant gain in correlation of genes associated with multiple aspects of airway epithelial inflammation including those related to extracellular matrix production and nitric oxide synthesis, and this change was associated with a poor clinical response to mepolizumab. These findings highlight that using differential gene correlation analysis offers insight into the molecular regulatory effects of treatment on gene interactions and may lead to better understanding of disease mechanisms and therapeutic responses. ClinicalTrials.gov ID: NCT03292588. |
| format | Article |
| id | doaj-art-b72fcb02eb9e4ba088b1e53d04fcdbee |
| institution | Directory of Open Access Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| spelling | doaj-art-b72fcb02eb9e4ba088b1e53d04fcdbee2025-09-07T11:24:10ZengNature PortfolioNature Communications2041-17232025-09-0116111610.1038/s41467-025-63629-2Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthmaCourtney L. Gaberino0R. Max Segnitz1Kimberly A. Dill-McFarland2Leonard B. Bacharier3Agustin Calatroni4Michelle A. Gill5Jeffrey Stokes6Andrew H. Liu7Robyn T. Cohen8Rajesh Kumar9Abigail Lang10Gurjit K. Khurana Hershey11Michael G. Sherenian12Edward M. Zoratti13Stephen J. Teach14Meyer Kattan15Patrice M. Becker16Alkis Togias17William W. Busse18Daniel J. Jackson19Matthew C. Altman20Department of Pediatrics, University of Wisconsin School of Medicine and Public HealthDepartment of Medicine, University of WashingtonDepartment of Medicine, University of WashingtonDepartment of Pediatrics, Monroe Carell Jr. Children’s Hospital at VanderbiltRho IncDepartment of Pediatrics, Washington UniversityDepartment of Pediatrics, Washington UniversityDepartment of Pediatrics, Children’s Hospital Colorado, University of Colorado School of MedicineDepartment of Pediatrics, Boston University School of MedicineDepartment of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of ChicagoDepartment of Pediatrics, Ann and Robert H. Lurie Children’s Hospital of ChicagoDepartment of Pediatrics, Cincinnati Children’s HospitalDepartment of Pediatrics, Cincinnati Children’s HospitalDepartment of Medicine, Henry Ford Health SystemChildren’s National HospitalDepartment of Pediatrics, Columbia UniversityNational Institute of Allergy and Infectious Diseases, National Institutes of HealthNational Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Pediatrics, University of Wisconsin School of Medicine and Public HealthDepartment of Pediatrics, University of Wisconsin School of Medicine and Public HealthDepartment of Medicine, University of WashingtonAbstract Mepolizumab (anti-IL5 therapy) reduces asthma exacerbations in urban children with exacerbation-prone eosinophilic asthma. We previously utilized nasal transcriptomics to identify inflammatory pathways (gene co-expression modules) associated with asthma exacerbations despite this therapy. In this study, we applied differential gene correlation analysis on these targeted gene co-expression modules to gain better insight into the treatment effects on correlation structure within gene networks. Mepolizumab treatment resulted in loss of correlation amongst eosinophil-specific genes but conservation and even strengthening of correlation amongst mast cell-specific genes, T2 cytokines, and airway epithelial inflammatory genes. Notably, mepolizumab induced significant gain in correlation of genes associated with multiple aspects of airway epithelial inflammation including those related to extracellular matrix production and nitric oxide synthesis, and this change was associated with a poor clinical response to mepolizumab. These findings highlight that using differential gene correlation analysis offers insight into the molecular regulatory effects of treatment on gene interactions and may lead to better understanding of disease mechanisms and therapeutic responses. ClinicalTrials.gov ID: NCT03292588.https://doi.org/10.1038/s41467-025-63629-2 |
| spellingShingle | Courtney L. Gaberino R. Max Segnitz Kimberly A. Dill-McFarland Leonard B. Bacharier Agustin Calatroni Michelle A. Gill Jeffrey Stokes Andrew H. Liu Robyn T. Cohen Rajesh Kumar Abigail Lang Gurjit K. Khurana Hershey Michael G. Sherenian Edward M. Zoratti Stephen J. Teach Meyer Kattan Patrice M. Becker Alkis Togias William W. Busse Daniel J. Jackson Matthew C. Altman Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma |
| title | Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma |
| title_full | Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma |
| title_fullStr | Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma |
| title_full_unstemmed | Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma |
| title_short | Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma |
| title_sort | mepolizumab alters gene regulatory networks of nasal airway type 2 and epithelial inflammation in urban children with asthma |
| url | https://doi.org/10.1038/s41467-025-63629-2 |
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