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IL-33 drives influe...
IL-33 drives influenza-induced asthma exacerbations by halting innate and adaptive antiviral immunity
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- Ravanetti, Lara (författare)
- Academic Medical Center of University of Amsterdam (AMC),University of Amsterdam
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- Dijkhuis, Annemiek (författare)
- Academic Medical Center of University of Amsterdam (AMC),University of Amsterdam
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- Dekker, Tamara (författare)
- Academic Medical Center of University of Amsterdam (AMC),University of Amsterdam
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- Sabogal Pineros, Yanaika S. (författare)
- University of Amsterdam,Academic Medical Center of University of Amsterdam (AMC)
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- Ravi, Abilash (författare)
- University of Amsterdam,Academic Medical Center of University of Amsterdam (AMC)
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- Dierdorp, Barbara S. (författare)
- University of Amsterdam,Academic Medical Center of University of Amsterdam (AMC)
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- Erjefält, Jonas S. (författare)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- Mori, Michiko (författare)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- Pavlidis, Stelios (författare)
- Imperial College London
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- Adcock, Ian M. (författare)
- Imperial College London
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- Rao, Navin L. (författare)
- Janssen Pharmaceuticals, US
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- Lutter, René (författare)
- University of Amsterdam,Academic Medical Center of University of Amsterdam (AMC)
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- Engelska.
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 143:4, s. 16-1370
- Relaterad länk:
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http://dx.doi.org/10...
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http://spiral.imperi...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Background: Influenza virus triggers severe asthma exacerbations for which no adequate treatment is available. It is known that IL-33 levels correlate with exacerbation severity, but its role in the immunopathogenesis of exacerbations has remained elusive. Objective: We hypothesized that IL-33 is necessary to drive asthma exacerbations. We intervened with the IL-33 cascade and sought to dissect its role, also in synergy with thymic stromal lymphopoietin (TSLP), in airway inflammation, antiviral activity, and lung function. We aimed to unveil the major source of IL-33 in the airways and IL-33–dependent mechanisms that underlie severe asthma exacerbations. Methods: Patients with mild asthma were experimentally infected with rhinovirus. Mice were chronically exposed to house dust mite extract and then infected with influenza to resemble key features of exacerbations in human subjects. Interventions included the anti–IL-33 receptor ST2, anti–TSLP, or both. Results: We identified bronchial ciliated cells and type II alveolar cells as a major local source of IL-33 during virus-driven exacerbation in human subjects and mice, respectively. By blocking ST2, we demonstrated that IL-33 and not TSLP was necessary to drive exacerbations. IL-33 enhanced airway hyperresponsiveness and airway inflammation by suppressing innate and adaptive antiviral responses and by instructing epithelial cells and dendritic cells of house dust mite–sensitized mice to dampen IFN-β expression and prevent the TH1-promoting dendritic cell phenotype. IL-33 also boosted luminal NETosis and halted cytolytic antiviral activities but did not affect the TH2 response. Conclusion: Interventions targeting the IL-33/ST2 axis could prove an effective acute short-term therapy for virus-induced asthma exacerbations.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Nyckelord
- airway hyperresponsiveness
- airways epithelial cells
- Asthma
- dendritic cells
- exacerbation
- IL-33
- immune response
- influenza
- NETosis
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Ravanetti, Lara
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Dijkhuis, Annemi ...
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Dekker, Tamara
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Sabogal Pineros, ...
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Ravi, Abilash
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Dierdorp, Barbar ...
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visa fler...
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Erjefält, Jonas ...
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Mori, Michiko
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Pavlidis, Stelio ...
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Adcock, Ian M.
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Rao, Navin L.
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Lutter, René
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Lungmedicin och ...
- Artiklar i publikationen
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Journal of Aller ...
- Av lärosätet
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Lunds universitet