title: L-Myc expression by dendritic cells is required for optimal T-cell priming.
abstract: 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 Mycl1(gfp) 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.
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Wumesh
authors: W
authors: KC
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Ansuman T
authors: AT
authors: Satpathy
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Aaron S
authors: AS
authors: Rapaport
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Carlos G
authors: CG
authors: Briseño
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Xiaodi
authors: X
authors: Wu
authors: Department of Medicine A, Hematology and Oncology, University of Muenster, 48149 Muenster, Germany.
authors: Jörn C
authors: JC
authors: Albring
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Emilie V
authors: EV
authors: Russler-Germain
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Nicole M
authors: NM
authors: Kretzer
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Vivek
authors: V
authors: Durai
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Stephen P
authors: SP
authors: Persaud
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Brian T
authors: BT
authors: Edelson
authors: Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.
authors: Jakob
authors: J
authors: Loschko
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Marina
authors: M
authors: Cella
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Paul M
authors: PM
authors: Allen
authors: Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.
authors: Michel C
authors: MC
authors: Nussenzweig
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Marco
authors: M
authors: Colonna
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Barry P
authors: BP
authors: Sleckman
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Theresa L
authors: TL
authors: Murphy
authors: 1] Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA [2] Howard Hughes Medical Institute, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
authors: Kenneth M
authors: KM
authors: Murphy
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002455:Cell Division; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D018116:Vesiculovirus / Q000276:immunology; D000099185:Interferon Regulatory Factor-8
chemical_list: D015703:Antigens, CD; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D039001:Integrin alpha Chains; D050835:Interferon Regulatory Factors; D016271:Proto-Oncogene Proteins c-myc; D000099185:Interferon Regulatory Factor-8; C587451:Mycl1 protein, mouse; C091367:alpha E integrins