Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development
By B. Cisse, M. Caton, M. Lehner, Takahiro Maeda, S. Scheu, R. Locksley, D. Holmberg, C. Zweier, N.S. den Hollander, S. Kant and 4 more. Cell, 2008
677 citations recorded by the source corpus.
Summary Plasmacytoid dendritic cells (PDC) 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 PDC. Constitutive or inducible deletion of murine E2-2 blocked the development of PDC 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.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/729353d1ad96be67a7f858b00d82a13b04c3bb5d
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Immunology
Citations in the corpus
- Plasmacytoid Dendritic Cells: Recent Progress and Open Questions (2011, background): “underlying the depletion, aberrant phenotype, and impaired function of pDCs in E2-2+/− mice and human patients (32).”