title: miR-9 enhances IL-2 production in activated human CD4(+)  T cells by repressing Blimp-1.
abstract: The fast production of effector cytokines, such as IL-2, is essential for the autocrine function in the rapid activation of naive CD4(+)  T cells. Here, we show that the microRNA (miRNA) pathway plays an important role in the posttranscriptional regulation of proinflammatory cytokines in human CD4(+)  T cells. miRNAs are small noncoding molecules that act as posttranscriptional regulators of gene expression by binding to the 3' untranslated region of target mRNAs. Using microarray and deep sequencing approaches, we detected an increase in the abundance of miR-9 in activated human CD4(+)  T cells. To determine the impact of miR-9 on immune responses, we analyzed its effect on two putative target genes, PRDM1, which encodes for the transcription factor Blimp-1 (B lymphocyte-induced maturation protein-1), and Bcl-6 (B cell lymphoma-6 protein). Suppression of miR-9 led to increased expression of PRDM1 and Bcl-6, which subsequently resulted in diminished secretion of IL-2 and IFN-γ. Our data provide evidence that the abundance of Blimp-1, and consequently the secretion of proinflammatory cytokines, is regulated in two ways: (i) transcriptional regulation by activation of CD4(+)  T cells and (ii) posttranscriptional regulation by enhanced miR-9 expression.
authors.affiliation: Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Thiele
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wittmann
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
authors.forename: Andreas
authors.initials: A
authors.lastname: Pahl
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D035683:MicroRNAs / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000096:biosynthesis*
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007376:Interleukin-2; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D007371:Interferon-gamma; D000074462:Positive Regulatory Domain I-Binding Factor 1