ArticleThe Journal of clinical investigation2015
High IFN-γ and low SLPI mark severe asthma in mice and humans.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 233 papers.
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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.
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Who cites it
233 citing papers in PubMed, 399 citations in OpenAlex.
- Airway remodelling rather than cellular infiltration characterizes both type2 cytokine biomarker-high and -low severe asthma.Allergy · 2022Trial
- The H3K27me3-NR1D1-IFN-γ axis in trained macrophages induced by early respiratory virus infection drives non-T2 asthma in children.Cellular & molecular immunology · 2026Article
- Platelet-derived serotonin epigenetically programs macrophage alternative activation to orchestrate type 2 airway inflammation.Cellular & molecular immunology · 2026Article
- Aberrant mucin expression and keratinization distinguishing severe from mild asthma revealed by interpretable machine learning.JCI insight · 2026Article
- Autophagy functions in lung macrophages and dendritic cells to regulate allergen-dependent inflammatory responses.Autophagy · 2026Article
- Update on environmental determinants of allergic diseases.The Journal of allergy and clinical immunology · 2026Review
- IL-9 and Blimp-1 protect the transcriptional identity of group 2 innate lymphocytes in allergic asthma.Nature immunology · 2026Article
- Establishment of an Autoimmune Premature Ovarian Insufficiency Mouse Model with Proteomic Analyses: An Exploratory Study.International journal of molecular sciences · 2026Article
- Sex Differences in Asthma Pathogenesis.Immunological reviews · 2026Review
- Pentraxin 3 deficiency exacerbates neutrophilic inflammation and airway hyperresponsiveness in type 2-low asthma.Frontiers in allergy · 2026Article
- Natural medicines for asthma management: mechanisms aligned with endotypes and multi-dimensional intervention.Frontiers in pharmacology · 2026Review
- Neutrophil Heterogeneity in Airway Inflammatory Diseases.Inflammation · 2025Review
- Immunotherapy for asthma.Cellular & molecular immunology · 2025Review
- The immunology of asthma and chronic rhinosinusitis.Nature reviews. Immunology · 2025Review
- Circadian Clock Disruption and Non-type 2 Asthma: A Hypothesis-Driven Perspective on Immune, Epithelial, and Steroid Response.Clinical reviews in allergy & immunology · 2025Review
- Recombinant BCG Expressing IL-12 as A Novel Immunomodulatory Strategy for Allergic Asthma: Opportunities and Challenges.Clinical reviews in allergy & immunology · 2025Review
- Biomarker-driven drug development for allergic diseases and asthma: An FDA public workshop.The Journal of allergy and clinical immunology · 2025Article
- Asthma Alleviation by Ginsenoside Rb1 via Promotion of Treg Proliferation and Inflammatory T Cell Inhibition.Allergy · 2025Article
- Asthma Phenotypes and Biomarkers.Respiratory care · 2025Review
- Rhinovirus as a driver of airway T cell dynamics in children with treatment-refractory recurrent wheeze.JCI insight · 2025Article
173 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Severe asthma (SA) is a challenge to control, as patients are not responsive to high doses of systemic corticosteroids (CS). In contrast, mild-moderate asthma (MMA) is responsive to low doses of inhaled CS, indicating that Th2 cells, which are dominant in MMA, do not solely orchestrate SA development. Here, we analyzed broncholalveolar lavage cells isolated from MMA and SA patients and determined that IFN-γ (Th1) immune responses are exacerbated in the airways of individuals with SA, with reduced Th2 and IL-17 responses. We developed a protocol that recapitulates the complex immune response of human SA, including the poor response to CS, in a murine model. Compared with WT animals, Ifng-/- mice subjected to this SA model failed to mount airway hyperresponsiveness (AHR) without appreciable effect on airway inflammation. Conversely, AHR was not reduced in Il17ra-/- mice, although airway inflammation was lower. Computer-assisted pathway analysis tools linked IFN-γ to secretory leukocyte protease inhibitor (SLPI), which is expressed by airway epithelial cells, and IFN-γ inversely correlated with SLPI expression in SA patients and the mouse model. In mice subjected to our SA model, forced SLPI expression decreased AHR in the absence of CS, and it was further reduced when SLPI was combined with CS. Our study identifies a distinct immune response in SA characterized by a dysregulated IFN-γ/SLPI axis that affects lung function.
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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.