BibTex format
@article{Ravanetti:2019:10.1016/j.jaci.2018.08.051,
author = {Ravanetti, L and Dijkhuis, A and Dekker, T and Sabogal, Pineros YS and Ravi, A and Dierdorp, BS and Erjefält, JS and Mori, M and Pavlidis, S and Adcock, IM and Rao, NL and Lutter, R},
doi = {10.1016/j.jaci.2018.08.051},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1355--1370},
title = {IL-33 drives influenza-induced asthma exacerbations by halting innate and adaptive anti-viral immunity},
url = {http://dx.doi.org/10.1016/j.jaci.2018.08.051},
volume = {143},
year = {2019}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BACKGROUND: Influenza virus triggers severe exacerbations of asthma for which no adequate treatment is available. It is known that IL-33 levels correlate with exacerbation severity, but its role in the immune-pathogenesis 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 TSLP, in airway inflammation, anti-viral 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 exacerbation. METHODS: Mild asthmatic patients were experimentally infected with rhinovirus. Mice were chronically exposed to house dust mite (HDM) extract and then infected with influenza to resemble key features of exacerbations in humans. Interventions included anti-IL-33-receptor ST2 and/or anti-TSLP. RESULTS: We identified bronchial ciliated cells and Type-II alveolar cells as a major local source of IL-33 during virus-driven exacerbation in humans and mice, respectively. By blocking ST2 we demonstrated that IL-33 and not TSLP was necessary to drive exacerbations. IL-33 enhanced AHR and airway inflammation by suppressing innate and adaptive anti-viral responses and by instructing epithelial cells and dendritic cells (DCs) of HDM-sensitized mice to dampen IFN-β expression and prevent the Th1-promoting DCs phenotype. IL-33 also boosted luminal NETosis and halted cytolytic anti-viral 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 exacerbation.
AU - Ravanetti,L
AU - Dijkhuis,A
AU - Dekker,T
AU - Sabogal,Pineros YS
AU - Ravi,A
AU - Dierdorp,BS
AU - Erjefält,JS
AU - Mori,M
AU - Pavlidis,S
AU - Adcock,IM
AU - Rao,NL
AU - Lutter,R
DO - 10.1016/j.jaci.2018.08.051
EP - 1370
PY - 2019///
SN - 0091-6749
SP - 1355
TI - IL-33 drives influenza-induced asthma exacerbations by halting innate and adaptive anti-viral immunity
T2 - Journal of Allergy and Clinical Immunology
UR - http://dx.doi.org/10.1016/j.jaci.2018.08.051
UR - https://www.ncbi.nlm.nih.gov/pubmed/30316823
UR - http://hdl.handle.net/10044/1/63948
VL - 143
ER -