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

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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- (Formula presented.) and IFN- (Formula presented.) -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.
Original languageEnglish
Article number2444
Issue number11
Publication statusPublished - 1 Nov 2022


  • asthma
  • case-control study
  • dynamics
  • exosome
  • longitudinal
  • microRNA
  • pulmonary
  • rhinovirus

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