ArticlePloS one2018
Human lung tissue provides highly relevant data about efficacy of new anti-asthmatic drugs.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 33 citations in OpenAlex.
- Elarekibep, an inhaled anti-IL-4 receptor alpha Anticalin, in moderate-to-severe asthma: a randomized, placebo-controlled phase 2a study (APATURA).Respiratory research · 2026Trial
- Effect of Dupilumab on Type 2 Biomarkers in Chronic Rhinosinusitis With Nasal Polyps: SINUS-52 Study Results.The Annals of otology, rhinology, and laryngology · 2023Trial
- Innate Immunity and Asthma Exacerbations: Insights From Human Models.Immunological reviews · 2025Review
- Cold storage of human precision-cut lung slices in TiProtec preserves cellular composition and transcriptional responses and enables on-demand mechanistic studies.Respiratory research · 2025Article
- Degradation of IL-4Ralpha by Immunoproteasome: implication in airway type 2 inflammation and hyperresponsiveness.Frontiers in immunology · 2025Article
- High prevalence and genetic diversity ofMicrobiology spectrum · 2024Article
- The disrupted molecular circadian clock of monocytes and macrophages in allergic inflammation.Frontiers in immunology · 2024Article
- Application of Precision-Cut Lung Slices as an In Vitro Model for Research of Inflammatory Respiratory Diseases.Bioengineering (Basel, Switzerland) · 2022Review
- The Challenge of Long-Term Cultivation of Human Precision-Cut Lung Slices.The American journal of pathology · 2022Article
- Rhinovirus-induced Human Lung Tissue Responses Mimic Chronic Obstructive Pulmonary Disease and Asthma Gene Signatures.American journal of respiratory cell and molecular biology · 2021Article
- Monocytes and Macrophages Serve as Potent Prostaglandin DInternational journal of molecular sciences · 2021Article
- A modified protocol for successful miRNA profiling in human precision-cut lung slices (PCLS).BMC research notes · 2021Article
- In Vitro Models for Studying Respiratory Host-Pathogen Interactions.Advanced biology · 2021Review
- Modifying and IntegratingFrontiers in bioengineering and biotechnology · 2020Review
- Heat shock protein 70 is a positive regulator of airway inflammation and goblet cell hyperplasia in a mouse model of allergic airway inflammation.The Journal of biological chemistry · 2019Article
- Transcriptomic Analysis Reveals Priming of The Host Antiviral Interferon Signaling Pathway by BronchobiniInternational journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Subgroups of patients with severe asthma are insensitive to inhaled corticosteroids and require novel therapies on top of standard medical care. IL-13 is considered one of the key cytokines in the asthma pathogenesis, however, the effect of IL-13 was mostly studied in rodents. This study aimed to assess IL-13 effect in human lung tissue for the development of targeted therapy approaches such as inhibition of soluble IL-13 or its receptor IL-4Rα subunit. Precision-cut lung slices (PCLS) were prepared from lungs of rodents, non-human primates (NHP) and humans. Direct effect of IL-13 on human lung tissue was observed on inflammation, induction of mucin5AC, and airway constriction induced by methacholine and visualized by videomicroscopy. Anti-inflammatory treatment was evaluated by co-incubation of IL-13 with increasing concentrations of IL-13/IL-13 receptor inhibitors. IL-13 induced a two-fold increase in mucin5AC secretion in human bronchial tissue. Additionally, IL-13 induced release of proinflammatory cytokines eotaxin-3 and TARC in human PCLS. Anti-inflammatory treatment with four different inhibitors acting either on the IL-13 ligand itself (anti-IL-13 antibody, similar to Lebrikizumab) or the IL-4Rα chain of the IL-13/IL-4 receptor complex (anti-IL-4Rα #1, similar to AMG 317, and #2, similar to REGN668) and #3 PRS-060 (a novel anticalin directed against this receptor) could significantly attenuate IL-13 induced inflammation. Contrary to this, IL-13 did not induce airway hyperresponsiveness (AHR) in human and NHP PCLS, although it was effective in rodent PCLS. Overall, this study demonstrates that IL-13 stimulation induces production of mucus and biomarkers of allergic inflammation in human lung tissue ex-vivo but no airway hyperresponsiveness. The results of this study show a more distinct efficacy than known from animals models and a clear discrepancy in AHR induction. Moreover, it allows a translational approach in inhibitor profiling in human lung tissue.
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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.