ArticleAmerican journal of respiratory and critical care medicine2016
Toll-like Receptor 7 Is Reduced in Severe Asthma and Linked to an Altered MicroRNA Profile.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 68 citations in OpenAlex.
- Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients.Respiratory research · 2017Trial
- Using cell-specific late-phase asthma mRNA biomarkers to repurpose drugs that concurrently reverse disease signatures across multiple immune cell-types.PLoS computational biology · 2026Article
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- Bronchial Asthma and COVID-19: Etiology, Pathological Triggers, and Therapeutic Considerations.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- miR-146a-3p as a potential novel therapeutic by targeting MBD2 to mediate Th17 differentiation in Th17 predominant neutrophilic severe asthma.Clinical and experimental medicine · 2023Article
- Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: a multicentre prospective study.The European respiratory journal · 2023Article
- Non-Coding RNAs in Pulmonary Diseases: Comparison of Different Airway-Derived Biosamples.International journal of molecular sciences · 2023Review
- Analysis of Exosomal MicroRNA Dynamics in Response to Rhinovirus Challenge in a Longitudinal Case-Control Study of Asthma.Viruses · 2022Article
- Identifying a novel serum microRNA biomarker panel for the diagnosis of childhood asthma.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Review
- Viral Infection and Airway Epithelial Immunity in Asthma.International journal of molecular sciences · 2022Review
- Role of microRNAs in type 2 diseases and allergen-specific immunotherapy.Frontiers in allergy · 2022Review
- Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.The Journal of allergy and clinical immunology · 2021Observational
- Circulating miRNAs-A potential tool to identify severe asthma risk?Clinical and translational allergy · 2021Article
- Impaired interferon-α expression in plasmacytoid dendritic cells in asthma.Immunity, inflammation and disease · 2021Article
- Early life microbial exposures and allergy risks: opportunities for prevention.Nature reviews. Immunology · 2021Review
- Interrupting the Conversation: Implications for Crosstalk Between Viral and Bacterial Infections in the Asthmatic Airway.Frontiers in allergy · 2021Review
- Emerging roles of microRNAs in the regulation of Toll-like receptor (TLR)-signaling.Frontiers in bioscience (Landmark edition) · 2021Article
- Role of Epigenetics in the Pathogenesis, Treatment, Prediction, and Cellular Transformation of Asthma.Mediators of inflammation · 2021Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleAsthma is one of the most common chronic diseases worldwide, and individuals with severe asthma experience recurrent exacerbations. Exacerbations are predominantly viral associated and have been linked to defective airway IFN responses. Ascertaining the molecular mechanisms underlying this deficiency is a major research goal to identify new therapeutic targets.
objectivesWe investigated the hypothesis that reduced Toll-like receptor 7 (TLR7)-derived signaling drove the impaired IFN responses to rhinovirus by asthmatic alveolar macrophages (AMs); the molecular mechanisms underlying this deficiency were explored.
methodsAMs were recovered from bronchoalveolar lavage from healthy subjects and patients with severe asthma. Expression of pattern-recognition receptors and microRNAs was evaluated by quantitative polymerase chain reaction and Western blotting. A TLR7-luciferase reporter construct was created to evaluate binding of microRNAs to the 3' untranslated region of TLR7. IFN production was measured by quantitative polymerase chain reaction and ELISA. MEASUREMENTS AND MAIN
resultsThe expression of TLR7 was significantly reduced in severe asthma AMs and was associated with reduced rhinovirus and imiquimod-induced IFN responses by these cells compared with healthy AMs. Severe asthma AMs also expressed increased levels of three microRNAs, which we showed were able to directly reduce TLR7 expression. Ex vivo knockdown of these microRNAs restored TLR7 expression with concomitant augmentation of virus-induced IFN production.
conclusionsIn severe asthma, TLR7 deficiency drives impaired innate immune responses to virus by AMs. Blocking a group of microRNAs that are up-regulated in these cells can restore antiviral innate responses, providing a novel approach for therapy in asthma.
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