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

• Published in: Nature immunology Vol. 15; no. 12; pp. 1162 - 1170
• Main Authors: Simpson, Laura J., Patel, Sana, Bhakta, Nirav R., Choy, David F., Brightbill, Hans D., Ren, Xin, Wang, Yanli, Pua, Heather H., Baumjohann, Dirk, Montoya, Misty M., Panduro, Marisella, Remedios, Kelly A., Huang, Xiaozhu, Fahy, John V., Arron, Joseph R., Woodruff, Prescott G., Ansel, Karl M.
• Format: Journal Article
• Language: English
• Published: 02.11.2014
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3026

MicroRNAs (miRNAs) exert powerful effects on immune function by tuning networks of target genes that orchestrate cell behavior. We sought to uncover miRNAs and miRNA-regulated pathways that control the T H 2 responses that drive pathogenic inflammation in asthma. Profiling miRNA expression in human airway-infiltrating T cells revealed miR-19a elevation in asthma. Modulating miR-19 activity altered T H 2 cytokine production in both human and mouse T cells, and T H 2 cell responses were markedly impaired in cells lacking the entire miR-17∼92 cluster. miR-19 promotes T H 2 cytokine production and amplifies PI(3)K, JAK-STAT, and NF-κB signaling by direct targeting of PTEN, SOCS1, and A20. Thus, miR-19a up regulation in asthma may be an indicator and a cause of increased T H 2 cytokine production in the airways.