ArticleThe Journal of clinical investigation2025
Cellular and molecular features of asthma mucus plugs provide clues about their formation and persistence.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Diet-Microbiome-Immune Interactions at the Gut Mucosa in Food Allergy: Mechanisms, Gaps, and Therapeutic Implications.Allergy · 2026Review
- MUC5B and MUC5AC function in combination to regulate mucociliary transport on human airway epithelium.bioRxiv : the preprint server for biology · 2026Article
- Restoring the Airway Barrier: How Targeting Eosinophilic Inflammation Shapes Epithelial Health and Clinical Remission in Asthma.Diagnostics (Basel, Switzerland) · 2026Review
- Chest CT imaging toward personalized management of chronic obstructive pulmonary disease, asthma, and bronchiectasis: pulmonologist perspectives.Japanese journal of radiology · 2026Review
- Airway mucus plugs in asthma and chronic obstructive pulmonary disease: pathobiology, imaging, and implications for clinical trials.American journal of respiratory and critical care medicine · 2026Review
- ERS Congress 2025: highlights from the Basic and Translational Sciences Assembly.ERJ open research · 2026Article
- TSLP impairs mucociliary transport by inhibiting JAK signaling in both central and peripheral airways.Pflugers Archiv : European journal of physiology · 2026Article
- Eosinophil Extracellular Traps in Health and Disease: From Host Defense to Chronic Inflammation.Biomedicines · 2026Review
- An Inverse Transwell Assay for Airway Mucus Barrier Function Reveals both Virus- and Mucin-Specific Impacts on Infection.bioRxiv : the preprint server for biology · 2026Article
- Contemporary Concise Review 2025: Asthma.Respirology (Carlton, Vic.) · 2026Review
- Multicellular crosstalk in neutrophilic asthma: unraveling the pathogenic web of steroid resistance and emerging precision therapies.Journal of translational medicine · 2026Review
- Airway mucins function as endogenous inhibitors of neutrophil extracellular traps.bioRxiv : the preprint server for biology · 2026Article
- Review
- Review
- Asthma endotypes and theratypes.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Mucus Plugs and Eosinophilic Inflammation: Expanding the Paradigm to COPD.The journal of allergy and clinical immunology. In practice · 2026Review
- Mucus plugs in chronic obstructive pulmonary disease are heterogeneous in size and shape and occur in relatively large airways.American journal of respiratory and critical care medicine · 2026Article
- Airway epithelial heterogeneity and mucus plugging in asthmatic bronchioles.American journal of respiratory and critical care medicine · 2026Article
- When asthmatic distal airways lose their identity: a new mechanism of mucus plugs pathogenesis.American journal of respiratory and critical care medicine · 2026Article
- Maintenance and disruption of mucous barrier homeostasis: the critical role of MUC5AC/MUC5B balance in airway diseases.Frontiers in medicine · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
BACKGROUNDMucus plugs form in acute asthma and persist in chronic disease. Although eosinophils are implicated in mechanisms of mucus pathology, many mechanistic details about mucus plug formation and persistence in asthma are unknown.METHODSUsing histology and spatial, single-cell proteomics, we characterized mucus-plugged airways from nontransplantable donor lungs of 14 patients with asthma (9 with fatal asthma and 5 with nonfatal asthma) and individuals acting as controls (10 with chronic obstructive pulmonary disease and 14 free of lung disease). Additionally, we used an airway epithelial cell-eosinophil (AEC-eosinophil) coculture model to explore how AEC mucus affects eosinophil degranulation.RESULTSAsthma mucus plugs were tethered to airways showing infiltration with innate lymphoid type 2 cells and hyperplasia of smooth muscle cells and MUC5AC-expressing goblet cells. Asthma mucus plugs were infiltrated with immune cells that were mostly dual positive for eosinophil peroxidase (EPX) and neutrophil elastase, suggesting that neutrophils internalize EPX from degranulating eosinophils. Indeed, eosinophils exposed to mucus from IL-13-activated AECs underwent CD11b- and glycan-dependent cytolytic degranulation. Dual-positive granulocytes varied in frequency in mucus plugs. Whereas paucigranulocytic plugs were MUC5AC rich, granulocytic plugs had a mix of MUC5AC, MUC5B, and extracellular DNA traps. Paucigranulocytic plugs occurred more frequently in (acute) fatal asthma and granulocytic plugs predominated in (chronic) nonfatal asthma.CONCLUSIONTogether, our data suggest that mucin-rich mucus plugs in fatal asthma form because of acute goblet cell degranulation in remodeled airways and that granulocytic mucus plugs in chronic asthma persist because of a sustaining niche characterized by epithelial cell-mucin-granulocyte cross-talk.FUNDINGNIH grants HL080414, HL107202, and AI077439.
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