A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production

Nat Immunol. 2014 Dec;15(12):1162-70. doi: 10.1038/ni.3026. Epub 2014 Nov 2.

Abstract

MicroRNAs (miRNAs) exert powerful effects on immunological function by tuning networks of target genes that orchestrate cell activity. We sought to identify miRNAs and miRNA-regulated pathways that control the type 2 helper T cell (TH2 cell) responses that drive pathogenic inflammation in asthma. Profiling miRNA expression in human airway-infiltrating T cells revealed elevated expression of the miRNA miR-19a in asthma. Modulating miR-19 activity altered TH2 cytokine production in both human and mouse T cells, and TH2 cell responses were markedly impaired in cells lacking the entire miR-17∼92 cluster. miR-19 promoted TH2 cytokine production and amplified inflammatory signaling by direct targeting of the inositol phosphatase PTEN, the signaling inhibitor SOCS1 and the deubiquitinase A20. Thus, upregulation of miR-19a in asthma may be an indicator and a cause of increased TH2 cytokine production in the airways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Asthma / genetics
  • Asthma / immunology*
  • Asthma / metabolism
  • Bronchoalveolar Lavage Fluid / cytology
  • Clinical Trials as Topic
  • Cytokines / biosynthesis*
  • Flow Cytometry
  • High-Throughput Screening Assays
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Mice
  • Mice, Transgenic
  • MicroRNAs / immunology*
  • Multiplex Polymerase Chain Reaction
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Up-Regulation

Substances

  • Cytokines
  • MIRN19 microRNA, human
  • MicroRNAs