Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma

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 and Matthew C. Altman
Additional contact information
Courtney L. Gaberino: University of Wisconsin School of Medicine and Public Health
R. Max Segnitz: University of Washington
Kimberly A. Dill-McFarland: University of Washington
Leonard B. Bacharier: Monroe Carell Jr. Children’s Hospital at Vanderbilt
Agustin Calatroni: Rho Inc
Michelle A. Gill: Washington University
Jeffrey Stokes: Washington University
Andrew H. Liu: University of Colorado School of Medicine
Robyn T. Cohen: Boston University School of Medicine
Rajesh Kumar: Ann and Robert H. Lurie Children’s Hospital of Chicago
Abigail Lang: Ann and Robert H. Lurie Children’s Hospital of Chicago
Gurjit K. Khurana Hershey: Cincinnati Children’s Hospital
Michael G. Sherenian: Cincinnati Children’s Hospital
Edward M. Zoratti: Henry Ford Health System
Stephen J. Teach: Children’s National Hospital
Meyer Kattan: Columbia University
Patrice M. Becker: National Institutes of Health
Alkis Togias: National Institutes of Health
William W. Busse: University of Wisconsin School of Medicine and Public Health
Daniel J. Jackson: University of Wisconsin School of Medicine and Public Health
Matthew C. Altman: University of Washington

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63629-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63629-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63629-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().