ArticleAmerican journal of respiratory and critical care medicine2014
Foxa3 induces goblet cell metaplasia and inhibits innate antiviral immunity.
Article in American journal of respiratory and critical care medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 136 citations in OpenAlex.
- Current smoking and COPD are associated with differentiation-dependent secretory and inflammatory programs in airway basal cells.Respiratory research · 2026Article
- The RNA-binding protein Imp1 promotes a Spdef transcriptional program and mucus fucosylation during necrotizing enterocolitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Th2 cytokine-induced mucociliary remodeling in chronic rhinosinusitis: implications for antiviral defense and epithelial function.Respiratory research · 2026Article
- Single-nucleus multi-omics analysis of mouse small-intestinal Lgr5+ cell populations reveals Foxa3-induced Paneth cell-lineage differentiation.Communications biology · 2026Article
- The RNA-binding protein Imp1 promotes a Spdef transcriptional program and mucus fucosylation during necrotizing enterocolitis.bioRxiv : the preprint server for biology · 2026Article
- The FOXA transcription factors in allergic airway disease and asthma.Frontiers in allergy · 2026Review
- Rhinovirus C15 infection induces airway epithelial cell remodeling and robust inflammatory responses: Potential implications for airway obstruction in children.Mucosal immunology · 2025Article
- A Novel Regulatory Role for RPS4Y1 in Inflammatory and Fibrotic Processes.International journal of molecular sciences · 2025Article
- KLF5 Shapes Developing Respiratory Tubules by Inhibiting Actin Asymmetry in Epithelial Cells.American journal of respiratory cell and molecular biology · 2025Article
- Mucins and Their Roles in Asthma.Immunological reviews · 2025Review
- Therapeutic targeting of the NOTCH1 and neddylation pathways in T cell acute lymphoblastic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Adaptation in the Alleyways: Candidate Genes Under Potential Selection in Urban Coyotes.Genome biology and evolution · 2025Article
- Exploration of common pathogenesis and candidate hub genes between HIV and monkeypox co-infection using bioinformatics and machine learning.Scientific reports · 2024Article
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- Interleukin 13-Induced Inflammation Increases DPP4 Abundance but Does Not Enhance Middle East Respiratory Syndrome Coronavirus Replication in Airway Epithelia.The Journal of infectious diseases · 2024Article
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- The Possible Roles of IL-4/IL-13 in the Development of Eosinophil-Predominant Severe Asthma.Biomolecules · 2024Review
- FOXA3 regulates cholesterol metabolism to compensate for low uptake during the progression of lung adenocarcinoma.PLoS biology · 2024Article
- The memory of airway epithelium damage in smokers and COPD patients.Life science alliance · 2024Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
rationaleGoblet cell metaplasia accompanies common pulmonary disorders that are prone to recurrent viral infections. Mechanisms regulating both goblet cell metaplasia and susceptibility to viral infection associated with chronic lung diseases are incompletely understood.
objectivesWe sought to identify the role of the transcription factor FOXA3 in regulation of goblet cell metaplasia and pulmonary innate immunity.
methodsFOXA3 was identified in airways from patients with asthma and chronic obstructive pulmonary disease. We produced transgenic mice conditionally expressing Foxa3 in airway epithelial cells and developed human bronchial epithelial cells expressing Foxa3. Foxa3-regulated genes were identified by immunostaining, Western blotting, and RNA analysis. Direct binding of FOXA3 to target genes was identified by chromatin immunoprecipitation sequencing correlated with RNA sequencing. MEASUREMENTS AND MAIN
resultsFOXA3 was highly expressed in airway goblet cells from patients with asthma and chronic obstructive pulmonary disease. FOXA3 was induced by either IL-13 or rhinovirus. Foxa3 induced goblet cell metaplasia and enhanced expression of a network of genes mediating mucus production. Paradoxically, FOXA3 inhibited rhinovirus-induced IFN production, IRF-3 phosphorylation, and IKKε expression and inhibited viral clearance and expression of genes required for antiviral defenses, including MDA5, RIG-I, TLR3, IRF7/9, and nuclear factor-κB.
conclusionsFOXA3 induces goblet cell metaplasia in response to infection or Th2 stimulation. Suppression of IFN signaling by FOXA3 provides a plausible mechanism that may serve to limit ongoing Th1 inflammation during the resolution of acute viral infection; however, inhibition of innate immunity by FOXA3 may contribute to susceptibility to viral infections associated with chronic lung disorders accompanied by chronic goblet cell metaplasia.
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