A microRNA upregulated in asthma airway T cells promotes T(H)2 cytokine production

作者：Simpson Laura J; Patel Sana; Bhakta Nirav R; Choy David F; Brightbill Hans D; Ren Xin; Wang Yanli; Pua Heather H; Saumjohann Dirk; Montoya Misty M; Panduro Marisella; Remedios Kelly A; Huang Xiaozhu; Fahy John V; Arron Joseph R; Woodruff Prescott G; Ansel K Mark^*

来源：Nature Immunology, 2014, 15(12): 1162-1170.

DOI：10.1038/ni.3026

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 (T(H)2 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 T(H)2 cytokine production in both human and mouse T cells, and TH2 cell responses were markedly impaired in cells lacking the entire miR-17 similar to 92 cluster. miR-19 promoted T(H)2 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 T(H)2 cytokine production in the airways.

• 出版日期2014-12