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

LJ Simpson, S Patel, NR Bhakta, DF Choy… - Nature …, 2014 - nature.com
LJ Simpson, S Patel, NR Bhakta, DF Choy, HD Brightbill, X Ren, Y Wang, HH Pua…
Nature immunology, 2014nature.com
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 …
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.
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