ArticleJournal of innate immunity2020
Tollip Inhibits ST2 Signaling in Airway Epithelial Cells Exposed to Type 2 Cytokines and Rhinovirus.
Article in Journal of innate immunity, 2020. 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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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Integrated network pharmacology, molecular docking, and experimental validation to reveal the potential mechanism of Ginsenoside Rg1 on chronic obstructive pulmonary disease.Scientific reports · 2026Article
- The Originally Established PBE Cell Line as a Reliable In Vitro Model for Investigating SIV Infection and Immunity.International journal of molecular sciences · 2025Article
- Comprehensive single-cell RNA-sequencing study of Tollip deficiency effect in IL-13-stimulated human airway epithelial cells.BMC research notes · 2025Article
- Degradation of IL-4Ralpha by Immunoproteasome: implication in airway type 2 inflammation and hyperresponsiveness.Frontiers in immunology · 2025Article
- The Effect of a TLR3 Agonist on Airway Allergic Inflammation and Viral Infection in Immunoproteasome-Deficient Mice.Viruses · 2024Article
- Cooperation of immune regulators Tollip and surfactant protein A inhibits influenza A virus infection in mice.Respiratory research · 2024Article
- Toll-interacting protein inhibits transforming growth factor beta signaling in mouse lung fibroblasts.FASEB bioAdvances · 2024Article
- TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide andJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Tollip interaction with STAT3: a novel mechanism to regulate human airway epithelial responses to type 2 cytokines.Respiratory research · 2022Article
- PHLDA1 Suppresses TLR4-Triggered Proinflammatory Cytokine Production by Interaction With Tollip.Frontiers in immunology · 2022Article
- Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.American journal of respiratory cell and molecular biology · 2021Review
- Toll-interacting protein impacts on inflammation, autophagy, and vacuole trafficking in human disease.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Once Upon a Time.Journal of innate immunity · 2021Article
- Innate Immunity of the Lung.Journal of innate immunity · 2020Article
- Rhinovirus and Innate Immune Function of Airway Epithelium.Frontiers in cellular and infection microbiology · 2020Review
- Year-Long Rhinovirus Infection is Influenced by Atmospheric Conditions, Outdoor Air Virus Presence, and Immune System-Related Genetic Polymorphisms.Food and environmental virology · 2019Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The negative immune regulator Tollip inhibits the proinflammatory response to rhinovirus (RV) infection, a contributor to airway neutrophilic inflammation and asthma exacerbations, but the underlying molecular mechanisms are poorly understood. Tollip may inhibit IRAK1, a signaling molecule downstream of ST2, the receptor of IL-33. This study was carried out to determine whether Tollip downregulates ST2 signaling via inhibition of IRAK1, but promotes soluble ST2 (sST2) production, thereby limiting excessive IL-8 production in human airway epithelial cells during RV infection in a type 2 cytokine milieu (e.g., IL-13 and IL-33 stimulation). Tollip- and IRAK1-deficient primary human tracheobronchial epithelial (HTBE) cells and Tollip knockout (KO) HTBE cells were generated using the shRNA knockdown and CRISPR/Cas9 approaches, respectively. Cells were stimulated with IL-13, IL-33, and/or RV16. sST2, activated IRAK1, and IL-8 were measured. A Tollip KO mouse model was utilized to test if Tollip regulates the airway inflammatory response to RV infection in vivo under IL-13 and IL-33 treatment. Following IL-13, IL-33, and RV treatment, Tollip-deficient (vs. -sufficient) HTBE cells produced excessive IL-8, accompanied by decreased sST2 production but increased IRAK1 activation. IL-8 production following IL-13/IL-33/RV exposure was markedly attenuated in IRAK1-deficient HTBE cells, as well as in Tollip KO HTBE cells treated with an IRAK1 inhibitor or a recombinant sST2 protein. Tollip KO (vs. wild-type) mice developed exaggerated airway neutrophilic responses to RV in the context of IL-13 and IL-33 treatment. Collectively, these data demonstrate that Tollip restricts excessive IL-8 production in type 2 cytokine-exposed human airways during RV infection by promoting sST2 production and inhibiting IRAK1 activation. sST2 and IRAK1 may be therapeutic targets for attenuating excessive neutrophilic airway inflammation in asthma, especially during RV infection.
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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.