@article{4056,
  keywords = {airway lung-chip, asthma exacerbation, immune response, organ-on-chip, rhinovirus},
  author = {Janna C. Nawroth and Carolina Lucchesi and Deion Cheng and Abhishek Shukla and Justin Ngyuen and Tanvi Shroff and Antonio Varone and Katia Karalis and Hyun-Hee Lee and Stephen Alves and Geraldine A. Hamilton and Michael Salmon and Remi Villenave},
  title = {A Microengineered Airway Lung Chip Models Key Features of Viral-induced Exacerbation of Asthma},
  abstract = {Viral-induced exacerbation of asthma remains a major cause of hospitalization and mortality. New human-relevant models of the airways are urgently needed to understand how respiratory infections may trigger asthma attacks and to advance treatment development. Here, we describe a new human-relevant model of rhinovirus-induced asthma exacerbation that recapitulates viral infection of asthmatic airway epithelium and neutrophil transepithelial migration, and enables evaluation of immunomodulatory therapy. Specifically, a microengineered model of fully differentiated human mucociliary airway epithelium was stimulated with IL-13 to induce a T-helper cell type 2 asthmatic phenotype and infected with live human rhinovirus 16 (HRV16) to reproduce key features of viral-induced asthma exacerbation. We observed that the infection with HRV16 replicated key hallmarks of the cytopathology and inflammatory responses observed in human airways. Generation of a T-helper cell type 2 microenvironment through exogenous IL-13 stimulation induced features of asthmatic airways, including goblet cell hyperplasia, reduction of cilia beating frequency, and endothelial activation, but did not alter rhinovirus infectivity or replication. High-resolution kinetic analysis of secreted inflammatory markers revealed that IL-13 treatment altered IL-6, IFN-λ1, and CXCL10 secretion in response to HRV16. Neutrophil transepithelial migration was greatest when viral infection was combined with IL-13 treatment, whereas treatment with MK-7123, a CXCR2 antagonist, reduced neutrophil diapedesis in all conditions. In conclusion, our microengineered Airway Lung-Chip provides a novel human-relevant platform for exploring the complex mechanisms underlying viral-induced asthma exacerbation. Our data suggest that IL-13 may impair the hosts’ ability to mount an appropriate and coordinated immune response to rhinovirus infection. We also show that the Airway Lung-Chip can be used to assess the efficacy of modulators of the immune response.},
  year = {2020},
  journal = {American Journal of Respiratory Cell and Molecular Biology},
  volume = {63},
  pages = {591-600},
  month = {2020-11},
  issn = {1044-1549},
  url = {https://www.atsjournals.org/doi/10.1165/rcmb.2020-0010MA},
  doi = {10.1165/rcmb.2020-0010MA},
}