ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Alternaria induces STAT6-dependent acute airway eosinophilia and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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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.
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Who cites it
68 citing papers in PubMed, 89 citations in OpenAlex.
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- Structural and functional analysis of the TGF-β mimic, TGM-2: an immunomodulatory helminth protein.Genes and immunity · 2026Article
- Innate airway immune response to fungal allergens.Frontiers in immunology · 2026Review
- Prior acute ozone injury dampens Th2 responses to subsequent repetitive ozone exposures in mice.Research square · 2025Article
- Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction.Frontiers in immunology · 2025Article
- Immunometabolic programming of macrophages in asthma pathogenesis and therapy.Frontiers in physiology · 2025Review
- Reactive Oxygen Species in Asthma: Regulators of Macrophage Polarization and Therapeutic Implications: A Narrative Review.Journal of asthma and allergy · 2025Review
- PIP-seq identifies novel heterogeneous lung innate lymphocyte population activation after combustion product exposure.Scientific reports · 2024Article
- Notch 2 signaling contributes to intestinal eosinophil adaptations in steady state and tissue burden following oral allergen challenge.Journal of leukocyte biology · 2024Article
- A scoping review: What are the cellular mechanisms that drive the allergic inflammatory response to fungal allergens in the lung epithelium?Clinical and translational allergy · 2023Article
- Resistin-like molecules: a marker, mediator and therapeutic target for multiple diseases.Cell communication and signaling : CCS · 2023Review
- RNA-binding protein RBM3 intrinsically suppresses lung innate lymphoid cell activation and inflammation partially through CysLT1R.Nature communications · 2022Article
- LKB1 deficiency upregulates RELM-α to drive airway goblet cell metaplasia.Cellular and molecular life sciences : CMLS · 2021Article
- ORMDL3 expression in ASM regulates hypertrophy, hyperplasia via TPM1 and TPM4, and contractility.JCI insight · 2021Article
- STAT6-Dependent Exacerbation of House Dust Mite-Induced Allergic Airway Disease in Mice by Multi-Walled Carbon Nanotubes.NanoImpact · 2021Article
- The Role of Hypoxia-Induced Mitogenic Factor in Organ-Specific Inflammation in the Lung and Liver: Key Concepts and Gaps in Knowledge Regarding Molecular Mechanisms of Acute or Immune-Mediated Liver Injury.International journal of molecular sciences · 2021Review
- Cyclic-di-GMP Induces STING-Dependent ILC2 to ILC1 Shift During Innate Type 2 Lung Inflammation.Frontiers in immunology · 2021Article
- Resistin family proteins in pulmonary diseases.American journal of physiology. Lung cellular and molecular physiology · 2020Review
- COX Inhibition IncreasesJournal of immunology (Baltimore, Md. : 1950) · 2020Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The fungal allergen, Alternaria, is specifically associated with severe asthma, including life-threatening exacerbations. To better understand the acute innate airway response to Alternaria, naive wild-type (WT) mice were challenged once intranasally with Alternaria. Naive WT mice developed significant bronchoalveolar lavage eosinophilia following Alternaria challenge when analyzed 24 h later. In contrast to Alternaria, neither Aspergillus nor Candida induced bronchoalveolar lavage eosinophilia. Gene microarray analysis of airway epithelial cell brushings demonstrated that Alternaria-challenged naive WT mice had a >20-fold increase in the level of expression of found in inflammatory zone 1 (FIZZ1/Retnla), a resistin-like molecule. Lung immunostaining confirmed strong airway epithelial FIZZ1 expression as early as 3 h after a single Alternaria challenge that persisted for ≥5 d and was significantly reduced in STAT6-deficient, but not protease-activated receptor 2-deficient mice. Bone marrow chimera studies revealed that STAT6 expressed in lung cells was required for epithelial FIZZ1 expression, whereas STAT6 present in bone marrow-derived cells contributed to airway eosinophilia. Studies investigating which cells in the nonchallenged lung bind FIZZ1 demonstrated that CD45(+)CD11c(+) cells (macrophages and dendritic cells), as well as collagen-1-producing CD45(-) cells (fibroblasts), can bind to FIZZ1. Importantly, direct administration of recombinant FIZZ1 to naive WT mice led to airway eosinophilia, peribronchial fibrosis, and increased thickness of the airway epithelium. Thus, Alternaria induces STAT6-dependent acute airway eosinophilia and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness. This may provide some insight into the uniquely pathogenic aspects of Alternaria-associated asthma.
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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.