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

Abstract

IMMUNOBIOLOGY Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function Isabelle Dunand-Sauthier,1 Marie-Laure Santiago-Raber,1 Leonardo Capponi,1 Charles E. Vejnar,2 Olivier Schaad,3 Magali Irla,1 Queralt Seguín-Este´vez,1 Patrick Descombes,3 Evgeny M. Zdobnov,2 Hans Acha-Orbea,4 and Walter Reith1 1Department of Pathology and Immunology, Faculty of Medicine, 2Swiss Institute of Bioinformatics, Department of Medical Genetics and Development, Faculty of Medicine, and 3Genomics Platform, National Centre of Competence in Research Frontiers in Genetics, University of Geneva, Geneva, Switzerland; and 4Department of Biochemistry, Faculty of Biology and Medicine, University of Lausanne, Epalinges, Switzerland MicroRNAs (miRNAs) are small, noncod- ing 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 sys- tem 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 de- tailed analysis of its expression and func- tion in human and mouse DCs. A strong increase in miR155 expression was found to be a general and evolutionarily con- served feature associated with the activa- tion 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 abil- ity of DCs to promote antigen-specific T-cell activation. Expression-profiling studies performed with miR155
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DCs and DCs overexpressing miR155, com- bined 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 func- tional defects exhibited by miR155
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DCs could be reproduced by deregulated c- Fos expression. These results indicate t

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