ArticleThe Journal of clinical investigation2015
Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
What it found
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The trial behind it
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Who cites it
112 citing papers in PubMed, 157 citations in OpenAlex.
- Natural Products Targeting Airway Inflammation and Mucus Hypersecretion: Molecular Mechanisms and Therapeutic Potential for Respiratory Health.Nutrients · 2026Review
- Review
- Epigenetic Dysregulation of the NKX2-1/SPDEF Axis Drives Persistent Goblet Cell Differentiation and Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease.Respirology (Carlton, Vic.) · 2026Article
- KCNJ2 is Required for NLRP3 Inflammasome Activation That Drives Allergic Airway Inflammation and Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Butyrate SilencesAllergy, asthma & immunology research · 2026Article
- Airway Goblet Metaplasia Resulting from YAP/TAZ Deletion Drives Pulmonary Inflammatory Responses.American journal of respiratory cell and molecular biology · 2026Article
- Transcriptional coordination in multicellular lineage differentiation during lung organogenesis: deciphering the role of epithelial cells as a microenvironmental regulatory hub.Frontiers in cell and developmental biology · 2026Review
- Identification and Validation of FOXK1-Related Biomarkers in Diabetic Retinopathy.International journal of general medicine · 2026Article
- Article
- The FOXA transcription factors in allergic airway disease and asthma.Frontiers in allergy · 2026Review
- Lack of SLC26A9-mediated chloride secretion causes mucus plugging and severe respiratory distress in neonatal mice.JCI insight · 2025Article
- Specialized gas-exchange endothelium of the zebrafish gill.bioRxiv : the preprint server for biology · 2025Article
- Next Decade Research in Asthma: Broad Omics-Based Exploration Versus Targeted Airway Epithelium Studies.Journal of clinical medicine · 2025Review
- Disruption of E-cadherin in the airway led to dysplastic stressed cells and asthma-like phenotypes.Developmental cell · 2025Article
- Pharmacological Gq targeting prevents asthmatic airway remodeling.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Airway sympathectomy attenuates inflammation, transcriptional ratios of Muc5ac and Muc5b, and airway mechanic deficits in mice delivered intranasal IL-13.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- ACE-2 blockade and TMPRSS2 inhibition mitigate SARS-CoV-2 severity following cigarette smoke exposure in airway epithelial cellsMolecular therapy. Nucleic acids · 2025Article
- A Novel Regulatory Role for RPS4Y1 in Inflammatory and Fibrotic Processes.International journal of molecular sciences · 2025Article
- 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
- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Epithelial cells that line the conducting airways provide the initial barrier and innate immune responses to the abundant particles, microbes, and allergens that are inhaled throughout life. The transcription factors SPDEF and FOXA3 are both selectively expressed in epithelial cells lining the conducting airways, where they regulate goblet cell differentiation and mucus production. Moreover, these transcription factors are upregulated in chronic lung disorders, including asthma. Here, we show that expression of SPDEF or FOXA3 in airway epithelial cells in neonatal mice caused goblet cell differentiation, spontaneous eosinophilic inflammation, and airway hyperresponsiveness to methacholine. SPDEF expression promoted DC recruitment and activation in association with induction of Il33, Csf2, thymic stromal lymphopoietin (Tslp), and Ccl20 transcripts. Increased Il4, Il13, Ccl17, and Il25 expression was accompanied by recruitment of Th2 lymphocytes, group 2 innate lymphoid cells, and eosinophils to the lung. SPDEF was required for goblet cell differentiation and pulmonary Th2 inflammation in response to house dust mite (HDM) extract, as both were decreased in neonatal and adult Spdef(-/-) mice compared with control animals. Together, our results indicate that SPDEF causes goblet cell differentiation and Th2 inflammation during postnatal development and is required for goblet cell metaplasia and normal Th2 inflammatory responses to HDM aeroallergen.
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