| Literature DB >> 18854153 |
Babacar Cisse1, Michele L Caton, Manfred Lehner, Takahiro Maeda, Stefanie Scheu, Richard Locksley, Dan Holmberg, Christiane Zweier, Nicolette S den Hollander, Sarina G Kant, Wolfgang Holter, Anita Rauch, Yuan Zhuang, Boris Reizis.
Abstract
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.Entities:
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Year: 2008 PMID： 18854153 PMCID： PMC2631034 DOI： 10.1016/j.cell.2008.09.016
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582