title: A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production.
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.
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Simpson
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Sana
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
authors.forename: Nirav R
authors.initials: NR
authors.lastname: Bhakta
authors.affiliation: Immunology, Tissue Growth, and Repair Biomarker Discovery, Genentech, South San Francisco, California, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Choy
authors.affiliation: Department of Immunology, Genentech, South San Francisco, California, USA.
authors.forename: Hans D
authors.initials: HD
authors.lastname: Brightbill
authors.affiliation: Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Ren
authors.affiliation: Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Pua
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Dirk
authors.identifier: 0000000183858288
authors.initials: D
authors.lastname: Baumjohann
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Misty M
authors.initials: MM
authors.lastname: Montoya
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Marisella
authors.initials: M
authors.lastname: Panduro
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Remedios
authors.affiliation: Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.affiliation: Immunology, Tissue Growth, and Repair Biomarker Discovery, Genentech, South San Francisco, California, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Arron
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
authors.affiliation: Department of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: K Mark
authors.initials: KM
authors.lastname: Ansel
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D057166:High-Throughput Screening Assays; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000276:immunology*; D060885:Multiplex Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C549214:MIRN19A microRNA, human; D035683:MicroRNAs