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Scientific article
English

Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function

Published inBlood, vol. 117, no. 17, p. 4490-4500
Publication date2011
Abstract

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate target mRNAs by binding to their 3' untranslated regions. There is growing evidence that microRNA-155 (miR155) modulates gene expression in various cell types of the immune system and is a prominent player in the regulation of innate and adaptive immune responses. To define the role of miR155 in dendritic cells (DCs) we performed a detailed analysis of its expression and function in human and mouse DCs. A strong increase in miR155 expression was found to be a general and evolutionarily conserved feature associated with the activation of DCs by diverse maturation stimuli in all DC subtypes tested. Analysis of miR155-deficient DCs demonstrated that miR155 induction is required for efficient DC maturation and is critical for the ability of DCs to promote antigen-specific T-cell activation. Expression-profiling studies performed with miR155(-/-) DCs and DCs overexpressing miR155, combined with functional assays, revealed that the mRNA encoding the transcription factor c-Fos is a direct target of miR155. Finally, all of the phenotypic and functional defects exhibited by miR155(-/-) DCs could be reproduced by deregulated c-Fos expression. These results indicate that silencing of c-Fos expression by miR155 is a conserved process that is required for DC maturation and function.

Keywords
  • Animals
  • Cell Differentiation/genetics/immunology
  • Cell Line
  • Dendritic Cells/cytology/physiology
  • Evolution, Molecular
  • Gene Silencing/immunology
  • Humans
  • Mice
  • Mice, Mutant Strains
  • MicroRNAs/genetics/immunology
  • Monocytes/cytology
  • Proto-Oncogene Proteins c-fos/genetics/immunology
  • RNA, Messenger/genetics/immunology
Citation (ISO format)
DUNAND-SAUTHIER, Isabelle et al. Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function. In: Blood, 2011, vol. 117, n° 17, p. 4490–4500. doi: 10.1182/blood-2010-09-308064
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Article (Published version)
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ISSN of the journal0006-4971
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