ArticleThe Journal of allergy and clinical immunology2014
Alternaria-derived serine protease activity drives IL-33-mediated asthma exacerbations.
Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
161 citing papers in PubMed, 248 citations in OpenAlex.
- Aspirin-Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2015Trial
- Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33.The Journal of allergy and clinical immunology · 2015Trial
- Structural and functional consequences of IL33 and IL1RL1 coding variants on IL-33/ST2 signaling.Genes and immunity · 2026Article
- Fungi in Asthma: From Epidemiology and Airway Mycobiome to Molecular Mechanisms and Novel Allergenic Phytopathogens.International journal of molecular sciences · 2026Review
- Fungal Sensitization and the Manifestation of Asthmatic Features in Chronic Obstructive Pulmonary Disease.Internal medicine (Tokyo, Japan) · 2026Article
- MyD88 mediates allergic airway inflammation by regulating ILC2s function through inducing the formation of P38/GATA3 complex.Respiratory research · 2026Article
- Fungal exposure exacerbates allergen-driven asthma in a two-hit mouse model.Respiratory research · 2026Article
- Tuft cells shape airway remodeling by eliciting OXGR1- and SOX9-dependent stem cell programs.Nature communications · 2026Article
- The context-dependent role of group 2 innate lymphoid cells in lung diseases.Acta biochimica et biophysica Sinica · 2026Review
- Concordance between different methods of detecting fungal-specific IgE antibody in asthma.Frontiers in allergy · 2026Article
- Animal models of fungus-related allergic airway disease: exposures, readouts, mechanisms, and translational gaps.Frontiers in cellular and infection microbiology · 2026Review
- Gut-Lung Microbiota Axis Shapes the Immune Microenvironment and Immunotherapeutic Response in Lung Cancer.International journal of biological sciences · 2026Review
- Innate airway immune response to fungal allergens.Frontiers in immunology · 2026Review
- The airway mycobiome in chronic respiratory diseases: current advances and future frontiers.Journal of translational medicine · 2025Review
- mTORC1 signaling in group 2 innate lymphoid cells coordinates neuro-immune crosstalk in allergic lung inflammation.Nature communications · 2025Article
- Article
- Article
- Targeting alarmins in asthma: From bench to clinic.The Journal of allergy and clinical immunology · 2025Review
- Characterisation ofJournal of fungi (Basel, Switzerland) · 2025Article
- IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential.Frontiers in immunology · 2025Review
101 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe fungal allergen Alternaria alternata is implicated in severe asthma and rapid onset life-threatening exacerbations of disease. However, the mechanisms that underlie this severe pathogenicity remain unclear.
objectiveWe sought to investigate the mechanism whereby Alternaria was capable of initiating severe, rapid onset allergic inflammation.
methodsIL-33 levels were quantified in wild-type and ST2(-/-) mice that lacked the IL-33 receptor given inhaled house dust mite, cat dander, or Alternaria, and the effect of inhibiting allergen-specific protease activities on IL-33 levels was assessed. An exacerbation model of allergic airway disease was established whereby mice were sensitized with house dust mite before subsequently being challenged with Alternaria (with or without serine protease activity), and inflammation, remodeling, and lung function assessed 24 hours later.
resultsAlternaria, but not other common aeroallergens, possessed intrinsic serine protease activity that elicited the rapid release of IL-33 into the airways of mice through a mechanism that was dependent upon the activation of protease activated receptor-2 and adenosine triphosphate signaling. The unique capacity of Alternaria to drive this early IL-33 release resulted in a greater pulmonary inflammation by 24 hours after challenge relative to the common aeroallergen house dust mite. Furthermore, this Alternaria serine protease-IL-33 axis triggered a rapid, augmented inflammation, mucus release, and loss of lung function in our exacerbation model.
conclusionAlternaria-specific serine protease activity causes rapid IL-33 release, which underlies the development of a robust TH2 inflammation and exacerbation of allergic airway disease.
Indexed as
Identifiers
What OpenQuestion holds
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.