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

Academic Article

Abstract

  • The transcription factors c-Myc and N-Myc - encoded by Myc and Mycn, respectively - regulate cellular growth1 and are required for embryonic development2,3. A third paralogue, Mycl1, is dispensable for normal embryonic development but its biological function has remained unclear4. 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 progenitor5 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 priming6. © 2014 Macmillan Publishers Limited. All rights reserved.
  • Authors

    Published In

  • Nature  Journal
  • Digital Object Identifier (doi)

    Author List

  • Wumesh KC; Satpathy AT; Rapaport AS; Briseño CG; Wu X; Albring JC; Russler-Germain EV; Kretzer NM; Durai V; Persaud SP
  • Start Page

  • 243
  • End Page

  • 247
  • Volume

  • 507
  • Issue

  • 7491