ArticleThe Journal of allergy and clinical immunology2017
Pulmonary ORMDL3 is critical for induction of Alternaria-induced allergic airways disease.
Article in The Journal of allergy and clinical immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 82 citations in OpenAlex.
- Decreased sphingolipid synthesis in children with 17q21 asthma-risk genotypes.The Journal of clinical investigation · 2020Trial
- PP4 deficiency drives airway epithelial senescence via the PERK-eIF2α-ATF4-p21 axis in severe asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Fungal exposure exacerbates allergen-driven asthma in a two-hit mouse model.Respiratory research · 2026Article
- ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Unconventional Activation of IRE1 Enhances Th17 Responses and Promotes Airway Neutrophilia.American journal of respiratory cell and molecular biology · 2024Article
- Unfolded protein response factor ATF6 augments T helper cell responses and promotes mixed granulocytic airway inflammation.Mucosal immunology · 2023Article
- ORMDL in metabolic health and disease.Pharmacology & therapeutics · 2023Review
- Neutrophilia in severe asthma is reduced in Ormdl3 overexpressing mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Association of childhood asthma with Gasdermin B (GSDMB) and Oromucoid-like 3 (ORMDL3) genes.Northern clinics of Istanbul · 2023Article
- Asthma Susceptibility GeneAmerican journal of respiratory cell and molecular biology · 2022Article
- Asthma and the Missing Heritability Problem: Necessity for Multiomics Approaches in Determining Accurate Risk Profiles.Frontiers in immunology · 2022Review
- Alt a 1 Promotes Allergic AsthmaFrontiers in immunology · 2022Article
- Sphingolipids and Asthma.Advances in experimental medicine and biology · 2022Article
- Orosomucoid-like protein 3, rhinovirus and asthma.World journal of critical care medicine · 2021Review
- Ameliorative effects of eosinophil deficiency on immune response, endoplasmic reticulum stress, apoptosis, and autophagy in fungus-induced allergic lung inflammation.Respiratory research · 2021Article
- Household mold exposure interacts with inflammation-related genetic variants on childhood asthma: a case-control study.BMC pulmonary medicine · 2021Article
- Role of unfolded proteins in lung disease.Thorax · 2021Review
- Respiratory Viral and Bacterial Factors That Influence Early Childhood Asthma.Frontiers in allergy · 2021Review
- The Impact of Endoplasmic Reticulum-Associated Protein Modifications, Folding and Degradation on Lung Structure and Function.Frontiers in physiology · 2021Review
- Experimental Mouse Models of Asthma and Analysis of CD4 T Cells.Methods in molecular biology (Clifton, N.J.) · 2021Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGenome-wide association studies have identified the ORM (yeast)-like protein isoform 3 (ORMDL3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma.
objectiveWe sought to investigate in vivo the functional role of ORMDL3 in disease inception.
methodsAn Ormdl3-deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata was determined. An adeno-associated viral vector was also used to reconstitute ORMDL3 expression in airway epithelial cells of Ormdl3 knockout mice.
resultsOrmdl3 knockout mice were found to be protected from developing allergic airways disease and showed a marked decrease in pathophysiology, including lung function and airway eosinophilia induced by Alternaria. Alternaria is a potent inducer of cellular stress and the unfolded protein response, and ORMDL3 was found to play a critical role in driving the activating transcription factor 6-mediated arm of this response through Xbp1 and downstream activation of the endoplasmic reticulum-associated degradation pathway. In addition, ORMDL3 mediated uric acid release, another marker of cellular stress. In the knockout mice, reconstitution of Ormdl3 transcript levels specifically in the bronchial epithelium resulted in reinstatement of susceptibility to fungal allergen-induced allergic airways disease.
conclusionsThis study demonstrates that ORMDL3, an asthma susceptibility gene identified by genome-wide association studies, contributes to key pathways that promote changes in airway physiology during allergic immune responses.
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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.