Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells

Immunity. 2010 Dec 14;33(6):905-16. doi: 10.1016/j.immuni.2010.11.023. Epub 2010 Dec 9.

Abstract

The interferon-producing plasmacytoid dendritic cells (pDCs) share common progenitors with antigen-presenting classical dendritic cells (cDCs), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of pDCs is actively maintained in the steady state. We report that the deletion of transcription factor E2-2 from mature peripheral pDCs caused their spontaneous differentiation into cells with cDC properties. This included the loss of pDC markers, increase in MHC class II expression and T cell priming capacity, acquisition of dendritic morphology, and induction of cDC signature genes. Genome-wide chromatin immunoprecipitation revealed direct binding of E2-2 to key pDC-specific and lymphoid genes, as well as to certain genes enriched in cDCs. Thus, E2-2 actively maintains the cell fate of mature pDCs and opposes the "default" cDC fate, in part through direct regulation of lineage-specific gene expression programs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / immunology
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Cell Differentiation* / genetics
  • Cell Differentiation* / immunology
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Cell Separation
  • Cell Transdifferentiation / genetics
  • Cell Transdifferentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Transcription Factor 4

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Tcf4 protein, mouse
  • Transcription Factor 4