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

Blood. 2011 Apr 28;117(17):4490-500. doi: 10.1182/blood-2010-09-308064. Epub 2011 Mar 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line
  • Dendritic Cells / cytology
  • Dendritic Cells / physiology*
  • Evolution, Molecular
  • Gene Silencing / immunology*
  • Humans
  • Mice
  • Mice, Mutant Strains
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Monocytes / cytology
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogene Proteins c-fos / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology


  • MIRN155 microRNA, human
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger