L-Myc expression by dendritic cells is required for optimal T-cell priming

L-Myc expression by dendritic cells is required for optimal T-cell priming

Nature 507, 7491 (2014). doi:10.1038/nature12967

Authors: Wumesh KC, Ansuman T. Satpathy, Aaron S. Rapaport, Carlos G. Briseño, Xiaodi Wu, Jörn C. Albring, Emilie V. Russler-Germain, Nicole M. Kretzer, Vivek Durai, Stephen P. Persaud, Brian T. Edelson, Jakob Loschko, Marina Cella, Paul M. Allen, Michel C. Nussenzweig, Marco Colonna, Barry P. Sleckman, Theresa L. Murphy & Kenneth M. Murphy

The transcription factors c-Myc and N-Myc—encoded by Myc and Mycn, respectively—regulate cellular growth and are required for embryonic development. A third paralogue, Mycl1, is dispensable for normal embryonic development but its biological function has remained unclear. To examine the in vivo function of Mycl1 in mice, we generated an inactivating Mycl1gfp allele that also reports Mycl1 expression. We find that Mycl1 is selectively expressed in dendritic cells (DCs) of the immune system and controlled by IRF8, and that during DC development, Mycl1 expression is initiated in the common DC progenitor concurrent with reduction in c-Myc expression. Mature DCs lack expression of c-Myc and N-Myc but maintain L-Myc expression even in the presence of inflammatory signals such as granulocyte–macrophage colony-stimulating factor. All DC subsets develop in Mycl1-deficient mice, but some subsets such as migratory CD103+ conventional DCs in the lung and liver are greatly reduced at steady state. Importantly, loss of L-Myc by DCs causes a significant decrease in in vivo T-cell priming during infection by Listeria monocytogenes and vesicular stomatitis virus. The replacement of c-Myc by L-Myc in immature DCs may provide for Myc transcriptional activity in the setting of inflammation that is required for optimal T-cell priming.

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