Journal
BLOOD
Volume 117, Issue 17, Pages 4490-4500Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-09-308064
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Funding
- Swiss National Science Foundation
- Geneva Cancer League
- Ernst and Lucy Schmidheiny Foundation
- Swiss Multiple Sclerosis Society
- National Center of Competence in Research on Neural Plasticity and Repair (NCCR-NEURO)
- European Union FP6 consortium
- Alliance for Lupus Research
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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. (Blood. 2011; 117(17):4490-4500)
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