ArticleJCI insight2021
Epithelial IL-33 appropriates exosome trafficking for secretion in chronic airway disease.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Mechanisms of the IL-33/ST2 Signaling Axis in Regulating Bone Metabolism.Biomolecules · 2026Review
- The role of extracellular vesicles in the transport and regulation of novel inflammatory mediators in IBD and its associated CRC.Frontiers in cell and developmental biology · 2026Review
- Beyond inhaled medications: precision medicine and biologic therapies targeting the IL-33/TSLP/type 2 axis in COPD.Frontiers in immunology · 2026Review
- Microbial sensing through the non-canonical inflammasome modulates airway type 2 immunity.Frontiers in immunology · 2026Article
- Senescence‑associated IL‑33 secretion undermines sorafenib efficacy in hepatocellular carcinoma via immune evasion.Oncology reports · 2025Article
- A translational view of airway epithelial dysfunction in COPD.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Mouse TThe Journal of allergy and clinical immunology · 2025Article
- EGF, TNF-α, and Hypoxia Preconditioning Enhances the Production and Therapeutic Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Regenerative Medicine.ACS biomaterials science & engineering · 2025Article
- HSP70 is a chaperone for IL-33 activity in chronic airway disease.JCI insight · 2025Article
- Involvement of lncRNA MIR205HG in idiopathic pulmonary fibrosis and IL-33 regulation via Alu elements.JCI insight · 2025Article
- Predictive value of serum interleukin-33 and thymic stromal lymphopoietin for the risk of acute exacerbation in patients with chronic obstructive pulmonary disease.Frontiers in medicine · 2025Article
- Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth.Cancer discovery · 2024Article
- Characterization of prostate macrophage heterogeneity, foam cell markers, and CXCL17 upregulation in a mouse model of steroid hormone imbalance.Scientific reports · 2024Article
- Review
- IL-33: Friend or foe in transplantation?The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Review
- BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells.Cellular & molecular immunology · 2024Article
- PROSTATE CELL HETEROGENEITY AND CXCL17 UPREGULATION IN MOUSE STEROID HORMONE IMBALANCE.bioRxiv : the preprint server for biology · 2024Article
- Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.JCI insight · 2024Article
- The ins-and-outs of exosome biogenesis, secretion, and internalization.Trends in cell biology · 2024Review
- The production, function, and clinical applications of IL-33 in type 2 inflammation-related respiratory diseases.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
IL-33 is a key mediator of chronic airway disease driven by type 2 immune pathways, yet the nonclassical secretory mechanism for this cytokine remains undefined. We performed a comprehensive analysis in human airway epithelial cells, which revealed that tonic IL-33 secretion is dependent on the ceramide biosynthetic enzyme neutral sphingomyelinase 2 (nSMase2). IL-33 is cosecreted with exosomes by the nSMase2-regulated multivesicular endosome (MVE) pathway as surface-bound cargo. In support of these findings, human chronic obstructive pulmonary disease (COPD) specimens exhibited increased epithelial expression of the abundantly secreted IL33Δ34 isoform and augmented nSMase2 expression compared with non-COPD specimens. Using an Alternaria-induced airway disease model, we found that the nSMase2 inhibitor GW4869 abrogated both IL-33 and exosome secretion as well as downstream inflammatory pathways. This work elucidates a potentially novel aspect of IL-33 biology that may be targeted for therapeutic benefit in chronic airway diseases driven by type 2 inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.