title: MicroRNA-directed program of cytotoxic CD8+ T-cell differentiation.
abstract: Acquisition of effector properties is a key step in the generation of cytotoxic T lymphocytes (CTLs). Here we show that inflammatory signals regulate Dicer expression in CTLs, and that deletion or depletion of Dicer in mouse or human activated CD8(+) T cells causes up-regulation of perforin, granzymes, and effector cytokines. Genome-wide analysis of microRNA (miR, miRNA) changes induced by exposure of differentiating CTLs to IL-2 and inflammatory signals identifies miR-139 and miR-150 as components of an miRNA network that controls perforin, eomesodermin, and IL-2Rα expression in differentiating CTLs and whose activity is modulated by IL-2, inflammation, and antigenic stimulation. Overall, our data show that strong IL-2R and inflammatory signals act through Dicer and miRNAs to control the cytolytic program and other aspects of effector CTL differentiation.
authors.affiliation: Signaling and Gene Expression Division, La Jolla Institute for Allergy and Immunology, San Diego, CA 92037.
authors.forename: Sara
authors.initials: S
authors.lastname: Trifari
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Pipkin
authors.forename: Hozefa S
authors.initials: HS
authors.lastname: Bandukwala
authors.forename: Tarmo
authors.initials: T
authors.lastname: Äijö
authors.forename: Jed
authors.initials: J
authors.lastname: Bassein
authors.forename: Runqiang
authors.initials: R
authors.lastname: Chen
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Martinez
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D054353:Perforin / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043244:Ribonuclease III / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D017931:DNA Primers; D053645:Interleukin-2 Receptor alpha Subunit; C546202:MIRN139 microRNA, mouse; D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse; D054353:Perforin; D043244:Ribonuclease III; D053804:Granzymes
keywords: CD8+ T-cell response; posttranscriptional regulation