title: MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production.
abstract: MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27, miRNAs coexpressed from two genomic clusters, which each functioned independently to limit interleukin-4 (IL-4) production. Mice lacking both clusters in T cells displayed increased Th2 cell responses and tissue pathology in a mouse model of asthma. Gene expression and pathway analyses placed miR-27 upstream of genes known to regulate Th2 cells. They also identified targets not previously associated with Th2 cell biology which regulated IL-4 production in unbiased functional testing. Thus, elucidating the biological function and target repertoire of miR-24 and miR-27 reveals regulators of Th2 cell biology.
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
authors: Heather H
authors: HH
authors: Pua
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
authors: David F
authors: DF
authors: Steiner
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
authors: Sana
authors: S
authors: Patel
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
authors: Jeanmarie R
authors: JR
authors: Gonzalez
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
authors: Jorge F
authors: JF
authors: Ortiz-Carpena
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
authors: Robin
authors: R
authors: Kageyama
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
authors: Ni-Ting
authors: NT
authors: Chiou
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
authors: Antonia
authors: A
authors: Gallman
authors: Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
authors: Dimitri
authors: D
authors: de Kouchkovsky
authors: Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
authors: Lukas T
authors: LT
authors: Jeker
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
authors: Michael T
authors: MT
authors: McManus
authors: Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
authors: David J
authors: DJ
authors: Erle
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco CA, USA. Electronic address: mark.ansel@ucsf.edu.
authors: K Mark
authors: KM
authors: Ansel
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D017423:Sequence Analysis, RNA; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; C540674:Mirn27 microRNA, mouse; D015847:Interleukin-4