Analysis of Exosomal MicroRNA Dynamics in Response to Rhinovirus Challenge in a Longitudinal Case-Control Study of Asthma
Wangfei Wang,
Anirban Sinha,
René Lutter,
Jie Yang,
Christian Ascoli,
Peter J. Sterk,
Nicole K. Nemsick,
David L. Perkins,
Patricia W. Finn
Affiliations
Wangfei Wang
Richard and Loan Hill Department of Biomedical Engineering, College of Engineering and Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
Anirban Sinha
Department of Pulmonary Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
René Lutter
Department of Pulmonary Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Jie Yang
Department of Mathematics, Statistics, and Computer Science, College of Liberal Arts and Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
Christian Ascoli
Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Peter J. Sterk
Department of Pulmonary Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Nicole K. Nemsick
Department of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
David L. Perkins
Division of Nephrology, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Patricia W. Finn
Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Asthma symptoms are often exacerbated by the common-cold-causing rhinovirus (RV). In this study, we characterized the temporal behavior of circulating exosomal microRNAs (ExoMiRNAs) in a longitudinal bi-phasic case-control study of mild asthmatics (n = 12) and matched non-atopic healthy controls (n = 12) inoculated with rhinovirus. We aimed to define clinical and immunologic characteristics associated with differentially expressed (DE) miRNAs. In total, 26 DE ExoMiRNAs, including hsa-let-7f-5p, hsa-let-7a-5p, hsa-miR-122-5p, hsa-miR-101-3p, and hsa-miR-126-3p, were identified between asthmatic and healthy subjects after inoculation with RV. Time series clustering identified a unique Cluster of Upregulated DE ExoMiRNAs with augmenting mean expression and a distinct Cluster of Downregulated DE ExoMiRNAs with mean expression decline in asthmatic subjects upon RV challenge. Notably, the Upregulated Cluster correlated with Th1 and interferon-induced cytokines/chemokines (IFN-γ and IFN-γ-inducible protein-10) and interleukin-10 (IL-10). Conversely, the Downregulated Cluster correlated with IL-13, a Th2 cytokine, pulmonary function measurements (FVC%, FEV1%, and PEF%), and inflammatory biomarkers (FeNO, eosinophil%, and neutrophil%). Key ExoMiRNA–target gene and anti-viral defense mechanisms of the Upregulated and Downregulated Clusters were identified by network and gene enrichment analyses. Our findings provide insight into the regulatory role of ExoMiRNAs in RV-induced asthma.
