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

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

Isabelle Dunand-Sauthier  1 , Marie-Laure Santiago-Raber, Leonardo Capponi, Charles E Vejnar, Olivier Schaad, Magali Irla, Queralt Seguín-Estévez, Patrick Descombes, Evgeny M Zdobnov, Hans Acha-Orbea, Walter Reith
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Free article

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

Isabelle Dunand-Sauthier et al. Blood. .
Free article

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.

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