MicroRNA-9 Fine-Tunes Dendritic Cell Function by Suppressing Negative Regulators in a Cell-Type-Specific Manner
Brendan Cordeiro,
Peter Jeon,
Giselle M. Boukhaled,
Mario Corrado,
Orsolya Lapohos,
Dominic G. Roy,
Kelsey Williams,
Russell G. Jones,
Samantha Gruenheid,
Selena M. Sagan,
Connie M. Krawczyk
Affiliations
Brendan Cordeiro
Department of Microbiology and Immunology, McGill University, Montreal, QC H3G 1Y6, Canada
Peter Jeon
Goodman Cancer Research Center, Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
Giselle M. Boukhaled
Goodman Cancer Research Center, Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
Mario Corrado
Goodman Cancer Research Center, Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
Orsolya Lapohos
Department of Microbiology and Immunology, McGill University, Montreal, QC H3G 1Y6, Canada
Dominic G. Roy
Goodman Cancer Research Center, Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
Kelsey Williams
Metabolic and Nutritional Programming Group, Van Andel Institute, 333 Bostwick Avenue NE, Grand Rapids, MI 49503, USA
Russell G. Jones
Goodman Cancer Research Center, Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada; Metabolic and Nutritional Programming Group, Van Andel Institute, 333 Bostwick Avenue NE, Grand Rapids, MI 49503, USA
Samantha Gruenheid
Department of Microbiology and Immunology, McGill University, Montreal, QC H3G 1Y6, Canada
Selena M. Sagan
Department of Microbiology and Immunology, McGill University, Montreal, QC H3G 1Y6, Canada
Connie M. Krawczyk
Department of Microbiology and Immunology, McGill University, Montreal, QC H3G 1Y6, Canada; Goodman Cancer Research Center, Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada; Metabolic and Nutritional Programming Group, Van Andel Institute, 333 Bostwick Avenue NE, Grand Rapids, MI 49503, USA; Corresponding author
Summary: Dendritic cells, cells of the innate immune system, are found in a steady state poised to respond to activating stimuli. Once stimulated, they rapidly undergo dynamic changes in gene expression to adopt an activated phenotype capable of stimulating immune responses. We find that the microRNA miR-9 is upregulated in both bone marrow-derived DCs and conventional DC1s but not in conventional DC2s following stimulation. miR-9 expression in BMDCs and conventional DC1s promotes enhanced DC activation and function, including the ability to stimulate T cell activation and control tumor growth. We find that miR-9 regulated the expression of several negative regulators of transcription, including the transcriptional repressor Polycomb group factor 6 (Pcgf6). These findings demonstrate that miR-9 facilitates the transition of DCs from steady state to mature state by regulating the expression of several negative regulators of DC function in a cell-type-specific manner.
