Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development

Cell. 2008 Oct 3;135(1):37-48. doi: 10.1016/j.cell.2008.09.016.


Plasmacytoid dendritic cells (PDCs) represent a unique immune cell type specialized in type I interferon (IFN) secretion in response to viral nucleic acids. The molecular control of PDC lineage specification has been poorly understood. We report that basic helix-loop-helix transcription factor (E protein) E2-2/Tcf4 is preferentially expressed in murine and human PDCs. Constitutive or inducible deletion of murine E2-2 blocked the development of PDCs but not of other lineages and abolished IFN response to unmethylated DNA. Moreover, E2-2 haploinsufficiency in mice and in human Pitt-Hopkins syndrome patients was associated with aberrant expression profile and impaired IFN response of the PDC. E2-2 directly activated multiple PDC-enriched genes, including transcription factors involved in PDC development (SpiB, Irf8) and function (Irf7). These results identify E2-2 as a specific transcriptional regulator of the PDC lineage in mice and humans and reveal a key function of E proteins in the innate immune system.

Publication types

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

MeSH terms

  • Adolescent
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Child
  • Child, Preschool
  • DNA-Binding Proteins
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Hyperventilation / immunology
  • Immunity, Innate
  • Intellectual Disability / immunology
  • Interferons / immunology
  • Mice
  • Nerve Tissue Proteins / immunology*
  • Syndrome
  • TCF Transcription Factors / immunology*
  • Transcription Factor 4
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • TCF Transcription Factors
  • TCF4 protein, human
  • TCF7L2 protein, human
  • Tcf4 protein, mouse
  • Tcf7l2 protein, mouse
  • Transcription Factor 4
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • Interferons

Associated data

  • GEO/GSE12505
  • GEO/GSE12507